When terrorist action releases a secret government virus in the Houston Federal building, the employees become aggressive and homicidal. Federal officials quarantine the building to wipe out the infected and control the story, but a small group of uninfected are fighting to get out.

An elite team of FBI profilers analyze the country's most twisted criminal minds, anticipating their next moves before they strike again. The Behavioral Analysis Unit's most experienced agent is David Rossi, a founding member of the BAU who returns to help the team solve new cases.

Deputy Police Chief Brenda Leigh Johnson transfers from Atlanta to LA to head up a special unit of the LAPD that handles sensitive, high-profile murder cases. Johnson's quirky personality and hard-nosed approach often rubs her colleagues the wrong way, but her reputation as one of the world's best interrogator eventually wins over even her toughest critics.