FBI agent Don Eppes recruits his younger brother, a brilliant mathematician, to help search for a serial rapist who has begun murdering his victims.

Don recruits Charlie to help figure out where a pair of serial bank robbers will strike next, but his accurate prediction fails to take into account the robbers' motives, and an agent is killed.

Don relies on Charlie's mathematical insight to help stop a deadly virus that may have been the product of an act of bioterrorism.

Charlie convinces Don to launch an investigation when an engineering student is found dead from an apparent suicide.

When a mathematician (Neil Patrick Harris) gets close to solving the Riemann hypothesis, a difficult math problem whose solution is worth millions, his daughter is kidnapped.

Don enlists Charlie to help stop a series of copycat railroad accidents involving negligence and an undecipherable numerical code.