The Sand ninja fight against time to treat Kankuro. Even the Sand’s poison expert, Granny Chiyo, is baffled. The only hope lies with the reinforcements sent by Tsunade.

Teams Kakashi and Guy reach the Akatsuki hideout. They hurry to infiltrate but are thwarted by a five-seal barrier. The only way to break the barrier is to remove all five seals at once.

Although stung with poison herself, Granny Chiyo uses the last of the antidote on Sakura. Mocking the tender scene between Granny Chiyo and Sakura, Sasori attempts to end Granny Chiyo's life.

Naruto, Choji and Shikamaru attempt to capture and interrogate Sai, but Sai withdraws after insulting Naruto. Shortly afterward, Ino appears. Concerned that the demon fox could fall into Akatsuki hands, the village elders challenge Tsunade's plan to send Naruto out of the village without the still bedridden Kakashi. Tsunade promises to protect Konoha with her own life if Naruto is captured, but is still forced to compromise with Danzo by adding Sai to Team Kakashi. She also temporarily replaces Kakashi with ANBU member Yamato and warns him to keep an eye on Sai. Naruto and Sakura finally meet their new team members, and Naruto is immediately angered upon Sai's appearance.

As Team Kakashi continues their search for Sasuke, Naruto suddenly collapses due to his previous fight with Orochimaru. As Naruto wakes up, Sai begins to reveal more about his brother, but Orochimaru suddenly attacks them. Sakura and Yamato come to Naruto's aid against Orochimaru, while Sai continues the search. Just as Sai finds Sasuke, Yamato finds Sai's bingo book with Sasuke listed as a target for assassination.

The temple monks explain that the tombs hold the loyal bodyguards of Fire Country's feudal lord. Naruto observes Sora sparring with other monks and becomes offended upon realizing he is holding back. Naruto challenges Sora, but just as the matter is about to get serious, another monk stops him. Naruto realizes Sora is despised by the other monks as he was himself and wishes to befriend him. Naruto visits Sora again and observes him practicing his wind jutsu in earnest, hoping to get strong enough to avenge his father. They later return to the temple to receive news that another tomb has been robbed.

The second stage of Naruto's training continues, while Tsunade sends out twenty teams composed of four ninja each to deal with the Akatsuki members in the Fire Country. Shikamaru leaves with Asuma, Izumo and Kotetsu, whereas Ino and Choji leave with Raido and Aoba. After putting in considerable effort, Naruto clears the second stage of his training, but collapses from hunger and exhaustion almost immediately afterward.

With careful planning, the group manages to find and trap Hidan and Kakuzu. However, things seem to be going a bit too smoothly.

Yukimaru informs Kakashi and the others to Naruto and Guren's whereabouts and they attempt to free them with Yukimaru's help. Kiba, Tenten and Lee once again battle Kihou, Kigiri and Nurari after gaining more power from Kabuto. Naruto and Guren continue to search for a way out, coming across human-sized Sanbi-like creatures and illusions. Will Naruto and Guren ever find a way out?

The second member of Sasuke's team is revealed to be a woman named Karin. After Sasuke and Suigetsu arrive at the Southern Hideout, Sasuke requests that Karin comes with them. Despite her hesitations and quarrels with Suigetsu, Karin ultimately accepts after remembering her very first encounter with Sasuke. Sasuke orders Suigetsu to release the prisoners, and after that, they set off to recruit the final member of the team - Jugo.

Sasuke's Sharingan proves to be superior against Deidara's explosives. Deidara creates one of his finest works, the C4 Karura, in order to take him down. What will Sasuke do now?

Jiraiya is now confronted by two new Pains who both possess different abilities than the one he was fighting. Just who is Pain and how many Pains are there?

Sakura reflects upon a time when she was infected with a strange disease by Naruto. In order to find a cure, an order was issued for Naruto to be quarantined at all costs before he could infect anybody else.

Kabuto attempts to bring Sasuke over to his side by pointing out that they both are fighting for the same goal: to bring down the Leaf Village. But Sasuke quickly rejects him.

Thanks to Itachi, the Reanimation Jutsu is released, and all the Reanimated Shinobi are returned to their resting places. But to everyone’s surprise, the real Madara still remains!

Orochimaru is forced to flee the Hidden Leaf after Third Hokage Hiruzen exposes his illegal experiments. Danzo, fearing that Orochimaru’s capture would lead to the exposure of his own involvement in the experiments, sends out one of his men to help.

Itachi Uchiha is inducted into Kakashi’s unit as the youngest member of the ANBU Black Ops. Itachi’s father, Fugaku, is pleased, thinking this will grant the Uchiha access to exclusive, top-secret Leaf intel.

The Ten Tails morphs into its final form, "The Divine Tree," and attacks the shinobi, absorbing their chakra one after another.