The story begins when high school student Kazuki Muto is killed one night saving a mysterious girl from a monster, only to wake up in his school dorm, believing it to have been a dream. However, he soon finds out that dream wasn't a dream at all when a giant serpentine monster attacks him and his sister. Tokiko Tsumura, the girl he saved, explains that the monster is a homunculus. Kazuki had been attacked and killed by it when he was rescuing her. However, she, feeling responsible for him, revived him by placing a Kakugane medallion in his chest, serving as a replacement heart. The Kakugane, as Tokiko explains, is an alchemical device that, when activated, takes a certain form based on the Kakugane's user, forming a unique Buso Renkin. The Buso Renkin is the only thing that can destroy a homunculus monster. Using this, Kazuki creates his own Buso Renkin (the "Sunlight Heart", a huge lance). Along with Tokiko and her own Buso Renkin (the "Valkyrie Skirt", an execution scythe), Kazuki joins the fight against the homunculi and their master.

The story begins when high school student Kazuki Muto is killed one night saving a mysterious girl from a monster, only to wake up in his school dorm, believing it to have been a dream. However, he soon finds out that dream wasn't a dream at all when a giant serpentine monster attacks him and his sister. Tokiko Tsumura, the girl he saved, explains that the monster is a homunculus. Kazuki had been attacked and killed by it when he was rescuing her. However, she, feeling responsible for him, revived him by placing a Kakugane medallion in his chest, serving as a replacement heart. The Kakugane, as Tokiko explains, is an alchemical device that, when activated, takes a certain form based on the Kakugane's user, forming a unique Buso Renkin. The Buso Renkin is the only thing that can destroy a homunculus monster. Using this, Kazuki creates his own Buso Renkin (the "Sunlight Heart", a huge lance). Along with Tokiko and her own Buso Renkin (the "Valkyrie Skirt", an execution scythe), Kazuki joins the fight against the homunculi and their master.