The Search for Tsunade Arc spans from chapters 139 to 171 of the manga and episodes 81 to 100 of the Naruto anime. The beginning of the arc is sometimes referred to as the "Return of Itachi Arc". The arc entails Naruto meeting the Akatsuki members Itachi Uchiha and Kisame Hoshigaki, his training to learn Rasengan, and meeting up with Tsunade. It also covers the battle between Orochimaru, Jiraiya and Tsunade. In the anime, discussion of Rock Lee's surgery takes place here instead of the Sasuke Retrieval Arc. This arc is preceded by the Invasion of Konoha Arc and is followed by the Sasuke Retrieval Arc in the manga and the Land of Tea Arc in the anime.
Return of Itachi
After Naruto defeated Gaara, helping save the village from destruction, Jiraiya was approached by Konoha's village elders, who asked Jiraiya to become the new Hokage. He respectfully declined the offer, feeling that, if he couldn't stop the Third Hokage from getting killed, he didn't deserve the title. Instead he offered to find his former team-mate and fellow Sannin, Tsunade, and ask her to become the new Hokage. Jiraiya then asked for one condition: that he could take Naruto along with him for extra training and for his protection. Jiraiya then approached Naruto at the Ramen Ichiraku, and asked him to accompany him on his journey. At first Naruto refused, and the only way he was able to convince Naruto to go with him was by telling Naruto that he could teach him a new jutsu which was stronger than Sasuke's Chidori. Naruto quickly agreed, and set out on the journey with him. The reason Jiraiya wanted to take him on his journey was so that he could protect Naruto from the Akatsuki, an organisation that was after the Nine-Tailed Demon Fox and the rest of the tailed beasts. Jiraiya wanted to make Naruto strong enough to eventually fight on his own against Akatsuki.
However, not everything went according to plan. Two strangers in black garb examined the damage to the village from a distance, having arrived shortly after Jiraiya and Naruto's departure with the purpose of searching for Naruto. Kakashi, waiting for Sasuke to finish his lunch, ran into Asuma and Kurenai in the middle of the village, in which they noticed the two strangers drinking tea nearby, having overheard the jōnin's conversation about Naruto's departure with Jiraiya. These two strangers started heading out of the village when they encountered Asuma and Kurenai.
The pair then introduced themselves: the larger one introduced himself as Kisame Hoshigaki, a missing-nin from Kirigakure. The other, more menacing one introduced himself as Itachi Uchiha and, after a short battle, Asuma and Kurenai learned that they were no match for these powerful adversaries. However, at the last moment, Kakashi arrived to assist in the battle. Kisame eagerly attempted to fight Kakashi, but Itachi cautioned that Kisame would not get away uninjured if he fought Kakashi head on, opting instead to take care of him himself. Itachi was so fast that the Jōnin couldn't see him forming any hand signs, and a battle of jutsu initiated soon after. Itachi then activated his Mangekyō Sharingan, and Kakashi was caught in Itachi's genjutsu, Tsukuyomi.
Tsukuyomi showed Kakashi tied to a plank of wood levitating over an endless ocean. Itachi then appeared in front of him and began to stab Kakashi with a sword. Then seemingly more clones appeared of Itachi with their own swords and began to stab Kakashi over and over again into what appeared to be three days, but, in actuality, only one second had passed. With Kakashi incapacitated, Kisame charged at the jōnin. Asuma and Kurenai were helpless until Might Guy appeared in a spectacular fashion, kicking Kisame away. Kisame was about to counter-attack, until Itachi declared that this fight had gone on for long enough, and that they weren't there to start a war, vanishing afterwards.
Naruto and Jiraiya made a stop at a post-station a short distance away from the village. While Kakashi was in the hospital, the jōnin were discussing why Itachi would come back to the village before figuring out that he was after Naruto, during which Sasuke walked in asking what had happened to Kakashi. Inadvertently, Sasuke learned that Itachi had come back to the village and was looking for Naruto. Sasuke hurried around the village, first going to Naruto's apartment, then the ramen shop, where he learned that Naruto had left with Jiraiya and that they had stopped at the post-station outside the village.
Sasuke started to run towards the station when Jiraiya eyed a beautiful woman and told Naruto to go back to the hotel room and practice moulding of chakra while Jiraiya took the woman out on a date. Sasuke reached the post-station but not before Itachi and Kisame found Naruto first. They forced Naruto out into the hallway and, right before Itachi and Kisame could take Naruto away, Sasuke appeared behind Itachi.
Sasuke glared at Itachi intensely, and Kisame noticed how much Sasuke and Itachi looked alike, prompting him to ask who he was. Itachi replied, "He's my younger brother." Sasuke activated his Chidori and declared, "I've lived my life like you told me to: I've resented you, and hated you, and now I am going to kill you," and then charged at Itachi. However, Itachi stopped Sasuke's Chidori, and broke Sasuke's wrist. Soon after this, Jiraiya appeared after being temporarily fooled by Itachi placing a genjutsu on the woman Jiraiya had taken out.
As Kisame held off the recently returned Jiraiya, Sasuke was nearly beaten to death, and Itachi used his Mangekyō Sharingan to injure Sasuke mentally using Tsukuyomi. Finally managing to intervene, Jiraiya used his Summoning: Toad Mouth Bind to force Itachi and Kisame to flee via Amaterasu. While Naruto and Jiraiya tended to Sasuke, Might Guy appeared to take Sasuke back to Konoha.
Later, Jiraiya told Naruto that the Akatsuki were after the Nine-Tails inside Naruto. Naruto understood that he must become stronger, so that he could protect himself and the people he cared about, and Naruto and Jiraiya resumed their search for Tsunade.
Search for Tsunade
The search for Tsunade led Naruto and Jiraiya to Tanzaku Town. At the same time, Orochimaru and Kabuto were also looking for Tsunade so that she could heal Orochimaru's arms. While Jiraiya prowled the town "looking for information" (or hitting on young ladies), Naruto practised the three steps required for learning the move that was stronger than Chidori: the Rasengan. The first step emphasised rotation, practised by trying to pop a water balloon. The second step was power, practised by exploding a rubber ball. The third step emphasised control, and the power and rotation in the first two steps must be used at 100%, while maintaining the ball of chakra inside a regular balloon without popping the balloon. When Naruto finished the first two steps, Jiraiya finally found out that Tsunade was at Tanzaku Town, and they headed out, with Naruto working on the third step along the journey.
When Jiraiya and Naruto finally arrived at Tanzaku Town, Orochimaru had already reached Tsunade first. Orochimaru offered Tsunade an exchange: if she healed Orochimaru's arms, Orochimaru would bring Tsunade's little brother and lover back to life using Summoning: Impure World Reincarnation. However, Tsunade must provide two human sacrifices. Orochimaru extended his deadline for her decision to a week, and left her to ponder the decision.
That night, Jiraiya and Naruto went to a bar to eat and find information about Tsunade, only to find Tsunade herself there, along with her assistant, Shizune. However, she declined Jiraiya's offer to become the Fifth Hokage, saying that only fools would want the title of Hokage. This irritated Naruto greatly, and Naruto and Tsunade headed outside to "fight". Tsunade easily handled Naruto using only one finger, but, when Naruto declared that it was his dream to become Hokage, Tsunade immediately saw the resemblance between Naruto and her brother and lover. Her reverie left Tsunade open, and Naruto took the opportunity to try to use Rasengan on her, although it was still incomplete. Upon seeing the Rasengan, Tsunade made a bet with him: if he could master Rasengan in a week, she would give him the necklace of the First Hokage. If he lost, she would confiscate his frog wallet and all its contents. Naruto accepted after learning the value of the necklace, and went away to train. Shizune was surprised that Tsunade had used the necklace in a bet, since the people that Tsunade had tried to give it to (her brother and her lover) had both died horribly the next day. Shizune explained this, and Naruto toughened his resolve to get it, not returning to the hotel at all for six days. On the sixth day, Shizune found Naruto unconscious and brought him back, and Naruto recovered after just a night's sleep because of the Nine-Tails' chakra. It was also during that night where Orochimaru dispatched Kabuto to assassinate Shizune to avoid any interference in his plan, and Shizune tried to stop Tsunade from going to meet Orochimaru, only to be knocked out by Tsunade.
Battle of the Sannin
Naruto woke up the next day to find out from Shizune that Tsunade was going to meet with Orochimaru, then Jiraiya arrived revealing that Tsunade had drugged his sake the previous night. Unaware that Kabuto was observing them and was surprised to find both Naruto and Jiraiya there, he chose to retreat just as the three rushed off to find her. Tsunade arrived, and attempted to secretly kill Orochimaru with her medical jutsu, only to be stopped by Kabuto himself revealing her intentions, as he was also a medical ninja. As Tsunade begins the fight Kabuto suggests to Orochimaru that they need to look for another place to fight before Tsunade can receive further aid, revealing that Jiraiya was nearby, so the two lured Tsunade to an open grass field to buy some time to capture her. Although at first she was able to hold Kabuto off, Kabuto was able to get the upper hand by exploiting Tsunade's hemophobia. That was when Jiraiya, Naruto, and Shizune arrived in time to stop Kabuto from killing Tsunade. Naruto was surprised to find Kabuto there and fighting Tsunade, but is quickly informed by Jiraiya that his headband clearly represents that Kabuto works for Orochimaru.
While Jiraiya tried his best to hold off Orochimaru, despite his handicap of being unable to fully control his chakra due to Tsunade's potion, Naruto and Shizune tried to protect Tsunade. Kabuto knocked out Shizune and proceeded to attack Tsunade, but Naruto intercepted him. Infuriated, Kabuto began to pummel Naruto, all the while telling Naruto that he was only a ninja by luck and that he could never dream of being on the same level as Sasuke. This only fuelled Naruto's resolve, and, when Kabuto charged at him with a kunai, Naruto allowed his hand to be impaled by the weapon, effectively holding Kabuto in position. He then used a shadow clone to mould chakra into his free hand, and hit Kabuto in the stomach with a fully formed Rasengan, which shocked both Tsunade and Orochimaru. The Rasengan was so powerful that, even with Kabuto's excellent regeneration ability, there was still too much damage for Kabuto to repair immediately. However, prior to getting hit by the Rasengan, Kabuto had severed Naruto's arteries leading to the heart, meaning that Naruto would soon die.
Touched by Naruto's resolution, Tsunade vowed to heal Naruto, as he couldn't recover by himself as the Nine-Tails' chakra couldn't be used if the heart's arteries were cut. Tsunade was able to heal Naruto, but Orochimaru realised that Naruto had become too powerful, and that his only chance to kill Naruto would be right now. Orochimaru lunged at Naruto with the Kusanagi sword, but Tsunade used her body to shield Naruto. When Orochimaru questioned her actions, she told Orochimaru that it was because Naruto would be the future Hokage, after which she determinedly announced, "And from today onwards, I too will put my life on the line to protect the Leaf, because I am the Fifth Hokage!" Tsunade then finally overcame her haemophobia.
Tsunade, Jiraiya, and Orochimaru all used the Summoning Technique, and they summoned Katsuyu the slug, Gamabunta the toad, and Manda the snake respectively. After a short battle between the summoned beasts, Tsunade was able to drive Gamabunta's sword down through Manda's mouth, leaving him pinned to the ground. Since Manda couldn't move anymore, he left. Tsunade then proceeded to beat up Orochimaru with her monstrous strength. Orochimaru admitted that his plan had failed, but warned Tsunade that he could still revive his arms using another technique, before leaving with Kabuto.
Tsunade then put her necklace on Naruto, saying that, just once more, she wanted to believe. When Naruto finally came around, the fight was over, and Gamabunta and Katsuyu were gone. Upon hearing that Tsunade had accepted the title of Fifth Hokage, Naruto proceeded to run down the reasons why she wasn't a good choice (and there were quite a few). Annoyed, Tsunade once again challenged Naruto to a fight outside. And, once again, she handled Naruto with ease, but, instead of flicking him away with a finger, she symbolically planted a kiss on his forehead, as she had done with Nawaki and Dan when she had given them the necklace, and told him that he would "make a fine man", whilst thinking to herself that he would make an excellent Hokage too. With that, Tsunade, Shizune, Jiraiya and Naruto headed back to Konoha.
The New Hokage
Upon their return, Naruto heard that the village of Konoha must continue their missions as normal. Iruka explained to Naruto (over a bowl of ramen, of course) that they must not show other villages that they were currently weak, so they must do as many missions as they had done before Orochimaru's invasion, even though their strength had been cut in half.
Tsunade was well-known as a great medical ninja, and she healed Sasuke and Kakashi of their ailments received during the fight with Itachi. She visited Lee (who was badly injured during his fight with Gaara in the Chūnin Exam preliminary round) after persistent nagging from many characters, and told him that he should give up being a ninja. There were fragments of bone in his spine, and the one operation that could be done (and could only be done by her) had a 50% chance of either curing or killing him.
Konohamaru, grandson of the Third Hokage, became upset at the thought of a new Hokage, especially a woman, and showed his anger by lashing out at his friends (including Naruto) and locking himself in Tsunade's new office. While this took place, Tsunade was introduced to the large amount of work required of a Hokage, and was reluctant at first, but found herself oddly interested in Lee's case. Konohamaru's friends, Moegi and Udon, along with Naruto, tried to find ways to get Konohamaru out, as he had set a great deal of obstacles leading to Tsunade's new office. Tsunade, who was looking for a book in her new office, managed to successfully get in, destroying all of Konohamaru's obstacles with her mighty strength. Naruto and Konohamaru were walking down the street and they overheard Shizune talking to Tsunade. They heard the Fifth Hokage state her concern and her motivation to help Lee. This convinced Konohamaru that Tsunade really was a good replacement for his grandfather.
Just minutes before Tsunade was inaugurated as the Fifth Hokage in front of the villagers, Shizune stumbled upon an open book on Tsunade's desk. It showed a series of mathematical equations surrounding a chart of a body. "50%" was written and crossed out, followed by an arrow pointing to a circle, which contained "58%", and Shizune could only smile.