NUMB3RS is a drama about an FBI agent who recruits his mathematical-genius brother to help the Bureau solve a wide range of challenging crimes in Los Angeles. The two brothers take on the most confounding criminal cases from a very distinctive perspective. Inspired by actual events, the series depicts how the confluence of police work and mathematics provides unexpected revelations and answers to the most perplexing criminal questions.

A dedicated FBI agent, Don Eppes (Rob Morrow), couldn't be more different from his younger brother, Charlie Eppes (David Krumholtz), a brilliant mathematician who, since he was little, yearned to impress his big brother. Don is joined on his team by fellow agents Megan Reeves (Diane Farr), a behavioral specialist who brings psychological insight to their investigations; David Sinclair (Alimi Ballard), who utilizes his incredible perspective and the survival skills he learned growing up in the Bronx; and new agent Colby Granger (Dylan Bruno) who just completed an extensive tour of duty in the U.S. Military.

After some initial reluctance, Don's team welcomes Charlie's innovative methods to crime-solving. Their father, Alan (Judd Hirsch), is happy to see his sons working together even though he doesn't understand the intricacies of what Charlie does for a living. It is his co-workers at CalSci who further refine Charlie's approach and help him stay focused. Physicist friend Dr. Larry Fleinhardt (Peter MacNicol) constantly challenges Charlie to employ a broader point of view to his work with the FBI, and Amita Ramanjuan (Navi Rawat), Charlie's former grad student, frequently helps him see cases in a new light Despite their disparate approaches to life, Don and Charlie are able to combine their areas of expertise and solve some killer cases.