One year after FBI Special Agent Clarice Starling rescued Catherine Martin from Buffalo Bill's basement, Attorney General Ruth Martin (Catherine's mother), sends Clarice on an urgent assignment to join the Violent Criminal Apprehension Program (VICAP) in the investigation of three new serial killings.

In order to prove to Krendler and the VICAP team that she is fit for duty, Clarice must find the psychological key that will unlock a confession from the suspect in the three river murders.