The film begins by revealing that an epidemic disease has overwhelmed humanity, turning nearly everyone into blood-thirsty zombies. According to the narrator, there is no known cure and very few survivors left fighting "Against the Dark". The first few scenes are used to establish the main characters, with Seagal playing a tough guy in charge of a group of zombie-hunters.
The survivors in the hospital are shown to be scared, isolated and untrusting. As the characters work their way through the hospital, they drift apart numerous times, often getting lost and attacked. (During one attack, the Wilhelm scream is heard briefly after Tao throws a zombie out of a window). To make matters worse for the survivors, a massive army base is planning to sterilize the area at dawn.
The survivors explain that there is only one functioning exit from the hospital (even though there seem to be numerous entrances through which they entered) and they have to get to this exit before the emergency power runs out and they are shut inside. To make matters worse many of the stairways and elevators are blocked off, forcing them to make their way level by level, finding a way to the next one down to gain the exit.