After a young heir named Shiki Tohno was involved in a major accident, he awoke in the hospital to discover that strange lines were imposed on the world around him, covering everything from living creatures like the doctors to inanimate objects such as his bed. Furthermore, he discovered that by cutting one of these lines, anything and anyone could be destroyed with frightening ease. With the world literally crumbling to dust around him, Shiki was on the verge of insanity when a self-styled "sorceress" appeared and gave him a special pair of spectacles that hid these "Lines of Death" from sight. After recovering in the hospital, Shiki was sent away to live with a branch family while his sister was raised as the new heir in his place.
Years later, Shiki is now a high-school student and living a normal life—that is, until he receives some devastating news: his father has died, and he must return to the main Tohno household at once. As Shiki settles into his new school and attempts to reconnect with his estranged family, he happens to meet a strange blonde-haired woman with piercing red eyes. Seized by an overwhelming bloodlust, Shiki regains his senses to find that he has savagely murdered the woman for no apparent reason. What force compelled him to carry out such an act, and how is it linked to his family's occult past and his "Mystic Eyes of Death Perception"? And... hang on, did that red-eyed lady just show up again looking no worse for wear? And does she have a crush on Shiki now?!
The Visual Novel contains five major story routes, each associated with one of the female leads. The routes are subdivided into two branches, Near and Far Side of the Moon: the Near Side routes (Arcueid—the aforementioned red-eyed lady—and Ciel) revolve around power struggles between various Nasuverse vampires and spend a lot of time on World Building; the Far Side routes (Akiha, Hisui, Kohaku), by contrast, are much more introverted and personal and focus on the dark secrets of the Tohno family. Each route except Kohaku's has two endings—usually labeled True and Good (except Akiha's, who only gets True and Normal)—and a secret epilogue, "Eclipse", is unlocked by clearing all nine endings.