Brilliant, but socially inept, forensic anthropologist Dr. Temperence Brennan in Bones Seasons 1-4 DVD Box set works at the Jeffersonian Institute in Washington DC. After consulting for him on a FBI case, she is approached by cocky yet charming ex-Arm Ranger turned Special Agent, Seeley Booth to help the Bureau solve crimes by identifying human remains that are too far gone for standard FBI forensic investigations. Brennan's empirical, literal view of the world causes friction with Booths emotive, instinctive attitude creating a volatile relationship. However as their case load increases the symbiotic partnership produces results and with the support of Brennan's Squint Squad, murderers, past and present should be on the look out.
 
The story of Bones Seasons 1-4 begins in the year 2005, and tells the story of a series of case files, solved weekly, by the unlikely alliance of Dr. Temperance "Bones" Brennan's forensic anthropology team at the Jeffersonian Institute (a thinly veiled allusion to the Smithsonian Institution) and FBI Special Agent Seeley Booth. By examining the human remains of the murder victims, Dr. Brennan and her team provide scientific expertise and an outsider's perspective to the world of criminal investigation to the FBI. In addition to the murder cases featured in each episode, the Bones Seasons 1-4 explore the backgrounds and relationships of the major characters including the developing friendship and possibly romantic relationship between Brennan and Booth. The Bones Seasons 1-4 DVD Box set shows some dark comedic undertones of the TV series.

Created by Hart Hanson, the Bones Seasons 1-4 on DVD Box set are very loosely based on the life of forensic anthropologist Kathy Reichs, who is a producer on the show. Its title character, Dr. Temperance "Bones" Brennan, is named after Temperance Brennan, the protagonist of Reichs' crime novel series. Bones Seasons 1-4 on this DVD Box set are a joint production by Josephson Entertainment, Far Field Productions and 20th Century Fox Television. The Bones series has also been renewed through its sixth season.