The show tells the story of a series of case files, solved weekly, by an unlikely alliance between Dr. Temperance Brennan's forensic anthropology team at the Jeffersonian Institution and FBI Special Agent Seeley Booth. By examining the human remains, namely bones, of the murder victims, Dr. Brennan's team provides scientific expertise and an outsider perspective to the world of criminal investigation to the FBI. In addition to the murder cases featured in each episode, the series explores the backgrounds and relationships of the major characters including the developing friendship between Brennan and Booth.

Brennan works at the Jeffersonian's Medico-Legal Lab in Washington DC. Aside from Booth, Brennan is most comfortable with her equally brilliant colleagues at the Jeffersonian's Medico-Legal Lab. Angela Montenegro an artist who specializes in reconstructing facial features and crime scenes, is Brennan's earthy and bawdy best friend; neophyte forensic anthropologist DR. Zack Addy , who has a genius IQ, is Brennan's socially awkward associate; "the bug guy," conspiracy theorist DR. Jack Hodgins, is an expert on insects, spores and minerals; and DR. Camille (Cam) Saroyan , the street-smart and centered coroner, must wrangle all the geniuses under her purview.