During their time away from the village, Shizune often worried about Tsunade's constant gambling, losing money and then borrowing more. She is not the type to tire easily and is very energetic and efficient while acting in her capacity of Hokage's Assistant, often urging Tsunade to finish the paperwork in order to avoid mountains of unsigned documents later on. Shizune is a fair-skinned woman of average height and slender build with black eyes and hair. During the Fourth Shinobi World War, she donned her standard shinobi attire, albeit with shorter sleeves this time. As Tsunade's first apprentice, Shizune is undoubtedly very capable kunoichi and a highly talented medical-nin. Shizune has rarely been seen in battle, but from what has been seen of her skills so far is that she incorporates the use of poison-related techniques during combat. In the anime, she has made use of the Shadow Clone Technique,[18] and has been shown to be able to create at least 36 clones at once.
When Orochimaru came to Tsunade years later in an attempt to get her to heal his arms, Tsunade turned him down and when Orochimaru refused to leave in Tsunade's count, Shizune clashed with Kabuto Yakushi for a brief moment. When Tsunade took on the title of Hokage, Shizune led a team consisting of Genma Shiranui, Raido Namiashi, and Iwashi Tatami to compensate for the lack of manpower caused by the Konoha Crush. In the anime, Shizune was defeated by Mizuki and the Legendary Stupid Brothers, the former who used her guise to lead Naruto and Iruka into a trap.
About two years after Naruto and Jiraiya left the village for training, Tsunade decided to host an early Chunin Exams to restore Konoha's reputation amongst the other villages. Ultimately, the Chunin Exams were ended early before starting the finals due to controversy happening in the second exam.
Shizune appears frequently in Part II, often being nearby Tsunade when she is issuing orders. Upon hearing the information that Sakura had gained from Sasori, she objects to sending Naruto on the mission to the Tenchi Bridge.
In the anime, Shizune was assigned to help seal the Three-Tails, being in charge of the sealing team, her assistants were Ino, Sakura and Hinata.
When Jiraiya comes in, he states that he has found the location of the Akatsuki's 'leader'. An apprentice of the legendary Sannin Tsunade, Shizune became a talented medical-nin under her tutelage; also becoming her companion during her sabbatical from active shinobi duty.
Some time after her uncle's death, Tsunade, his lover, left Konoha and Shizune went with Tsunade as her attendant and apprentice.
In the anime, on one such occasion when they were at a gambling den, they were approached by the Fourth Raikage and Amai who beseeched Tsunade to help their injured comrade. As a result, she is the one who tends to stress over details, such as Tsunade's tendency to gamble and to think with her heart.
She is often seen asking Tsunade questions about what to do with the village and the shinobi on missions. Her hair is straight and shoulder-length with bangs that cover her ears and frame her face.

She also wore the forehead protector of the Allied Shinobi Forces and a band around her right arm signifying her position. Her prowess set a high standard for Tsunade's other disciples, as the Sannin noted that she had not seen someone with so much skill since Shizune while training Sakura Haruno.[8] Shizune's chakra control is great enough to perform even the most complex medical ninjutsu, leading Tsunade to have the utmost confidence in her. She also demonstrated capable skills in fuinjutsu, able to lead her team in the process of sealing a tailed beast.
Orochimaru bribed Tsunade that if she helped, he would bring her brother and lover back to life and was given a week to think about it, but Shizune attempted to persuade Tsunade against it, even trying to convince Tsunade to kill him with her assistance. When Senta and Bunzo had stolen the First Hokage's necklace which was currently worn by Naruto, the two plot to blackmail Tsunade to give them the money she owes their boss.
While in a forest recuperating from the seemingly tiring mission, they detected a presence close by. After the uprising in the Land of Vegetables and the caravan that Naruto Uzumaki, Choji Akimichi, and Hinata Hyuga were guarding was connected, Tsunade sent Shizune to gather every available ninja and head over to the Land of Vegetables immediately.
During a meeting between Konoha and the Suna in hopes of getting their support, Shizune presented the files from the previous exams. Instead, it was decided by Gaara that a report on each participant would be sent to their respective village leader for them to decide if they would be promoted. However, Tsunade tells her than she and Sakura are two of the few shinobi she can trust in completely so she had to send Team Kakashi. After hearing this, Shizune suggested that they formulated an immediate surprise attack, should Jiraiya's information pan out. After Tsunade is persuaded to return to Konoha to become its Fifth Hokage, Shizune assumes the role of her assistant — a role she would retain long after Tsunade retired from the post. The bond between Tsunade and Shizune is strong and, above all, the latter sees her purpose in life as caring for Tsunade.
After Tsunade complied, Shizune was actually the one to conduct the surgery, and when she told the Raikage of her master's two great losses, upon hearing his response that her master was unhinged, she chided the Raikage, throwing the Exploding Insect. In an omake, she has shown she is a bit jealous of kunoichi like Tsunade and Kurenai Yuhi, complaining about their assets compared to her own. Normally, Shizune is seen in a long bluish-black kimono with white trimmings, held closed by a white obi, and open-toed sandals with low heels. Beneath this, she wears mesh armour, which is partially exposed on her sleeveless left-hand-side. When all attempts to persuade Tsunade failed, Shizune tried to use force to stop her from helping Orochimaru, although Tsunade easily defeated her. When Shizune found the note, she couldn't find Tsunade anywhere which left her the choice to use the Transformation Technique to pose as Tsunade.
As Raido and Genma leave to check out what is was, Shizune and Iwashi waited for their return. While Naruto was fighting Renga, Shizune, Shikamaru Nara and the other shinobi sent with her rescued Choji, Hinata, and Yurinojo from the ninja on Renga's side. As Tsunade made her true intention revealed of luring out the Akatsuki, Gaara, now the Kazekage, insisted that the exams be held within his village.

Shizune then insists if that's the case then her team could be sent instead, but Tsunade tells her that it wouldn't be the same as Sakura and Naruto had a personal stake in the mission.
The sealing however, was repeatedly interrupted by Guren and her men, and the sealing was instead left to Anbu members. Shizune has also been seen wearing the standard Konoha shinobi outfit complete with flak jacket, when deployed on missions which has distinct, extra-long sleeves. Later, she fought Kabuto again in an effort to protect an incapacitated Tsunade and Naruto Uzumaki. When Naruto and the Akagi brothers stole the bag, Shizune in Tsunade's form goes after them. When the duo took too long to return, Shizune and Iwashi went to see what was taking so long. Still worried about Naruto's safety she tries once again to plea with her not to send him unbeknownst to her that he was eavesdropping on the conversation until Tsunade acknowledges his presence.
She is a very kind and calm person but will immediately rush to Tsunade's aid and in contrast, will become fierce and somewhat ruthless; a testament of her loyalty to Tsunade.
Despite Shizune's efforts, Kabuto proved too much for her, as he managed to dodge her attacks and incapacitate her as well. Later when the Konoha Council asks to speak with Tsunade, it is revealed that Shizune had shared her uneasiness with Naruto constantly going up against members of Akatsuki that wanted to capture him. At the same time however, she is not timid and is not afraid of objecting to Tsunade's decisions or voicing her opinion as seen when she even alerted the Konoha Council to Tsunade's intention to send Naruto on a mission that Shizune thought would put him in great peril.
Shizune was able to heal her legs, and left the field of battle with the unconscious Naruto as the three Sannin prepared to conclude their battle. Acting immediately, Shizune gave them medical attention but noted that they needed to be hospitalised.
She has a great sense of morale and ethics, as she tried to persuade Tsunade from accepting Orochimaru's offer to heal his arms in exchange of reviving Dan and Nawaki, believing the said two would not be happy to return at the cost of innocent lives. She then returned to Konoha with Tsunade after she accepted the office of the Fifth Hokage. With help from Jirocho Wasabi (whom Tsunade encountered in the casino), Tsunade explained that she already paid her debt to the Akagi the year before. Later, when the Sasuke Recovery Team returned to the village, Shizune led a team of medical-nin including Kito and Mogusa. As the operation went on, Shizune noted that even though they were using Neji's hair as a medium to heal the wounds, that every strand of hair had to be affected by chakra control.

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