Highschool of the Dead is set in the present day, beginning as the world is struck by a deadly pandemic that turns humans into zombies, euphemistically referred to by the main characters as "Them" .
The story follows a group of high school students, the high school's nurse, and a young girl as they fight their way to safety through the deadly streets of Japan during a worldwide catastrophic event known as the "Outbreak". Led by sophomore Takashi Komuro, the local group of survivors consists of six others and a small dog, and creating a gestalt team with one purpose: to survive. The authors used role-playing terminology to categorize the specific attributes each character brings to the group. Takashi Komuro serves mainly as the team leader. Rei Miyamoto, Saeko Busujima, and Kohta Hirano are considered fighters because of their exceptional skills with weapons; Saya Takagi described as the wizard due to her intelligence and deduction skills; Shizuka Marikawa assigned the role of priest as she is a licensed physician.
The plot is initially concerned with survival and escape from the titular high school and zombies, but as the series proceeds it introduces the additional threats including: societal collapse, in the form of dangerous fellow survivors, technological attacks, using a Electromagnetic pulse bomb, and the possible decay of the characters' own moral codes.
