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In the series’ continuity, there are curious creatures that have the ability to grant young girls any wish they desire. However, in exchange for having their wish granted, that girl must become a magical girl tasked with the duty of fighting against witches, evil beings born from despair that are responsible for unexplained accidents, murders and suicides.

In the city of Mitakihara, the incubator Kyubey encounters a 14-year old girl named Madoka Kaname and her best friend Sayaka Miki. This small, cat-like creature offers a contract in which a girl can have any wish granted in exchange for becoming a magical girl tasked with fighting against witches. Meanwhile, a transfer student named Homura Akemi tries to stop Madoka from becoming a magical girl at all costs. As Madoka contemplates becoming a magical girl, she learns that a magical girl’s life is not as glamorous as she thought and is filled with anguish, suffering and despair. Madoka soon learns that not only do magical girls give up their souls to form their Soul Gems, the source of their magic, but when those Soul Gems become too tainted with despair, they transform into the very witches they fight against. She also learns that Homura is a magical girl from a different timeline who had repeated the same month countless times in order to try and save Madoka from a grisly fate. Learning all of this, Madoka decides to become a magical girl with the wish to stop witches before they are created, which rewrites the laws of the universe, resulting in Madoka becoming nothing more than a concept and Homura being the only one who remembers her in the new world that is formed.

The third film, Rebellion, takes place after the series and focuses on Homura as she deals with the loneliness of being separated from Madoka. The spin-off manga, Puella Magi Kazumi Magica: The Innocent Malice, is set in Asunaru City and follows an amnesiac magical girl named Kazumi who, along with a band of other magical girls known as the Pleiades Saints, starts to discover the dark nature of magical girls as she regains her memories. Puella Magi Oriko Magica takes place in an alternate timeline to the main series, in which Homura, Mami Tomoe and Kyōko Sakura, along with a young orphaned girl named Yuma Chitose who was abused as a child by her mother, find themselves up against a magical girl pair, Oriko Mikuni and Kirika Kure, who are hunting other magical girls. The story has two spin-off series, Noisy Citrine, which serves as a prequel, and Symmetry Diamond, which takes place in an alternate timeline. Puella Magi Madoka Magica: The Different Story also takes place in an alternate timeline, mainly focusing on the relationship between Mami and Kyōko.