A television reporter and her cameraman are trapped inside a building quarantined by the CDC after the outbreak of a mysterious virus which turns humans into bloodthirsty killers.

Adrian Monk was once a rising star with the San Francisco Police Department, legendary for using unconventional means to solve the department's most baffling cases. But after the tragic (and still unsolved) murder of his wife Trudy, he developed an extreme case of obsessive-compulsive disorder. Now working as a private consultant, Monk continues to investigate cases in the most unconventional ways.