Bones is an investigative drama following the exploits of Dr. Temperance Brennan (Emily Deschanel), a top forensic anthropologist. Dr. Brennan heads up a team at the Jeffersonian Institute that works to identify remains that cannot otherwise be identified by traditional means. She also works hand-in-hand with law enforcement organizations, using her unique talents to see past the obvious and find the hidden clues others may not see.

Special Agent Seeley Booth (David Boreanaz), a former Army Ranger Sniper working in the FBI's Homicide Investigations Unit, teams up with Dr. Brennan, or "Bones" as he soon nicknames her, and they often clash on how best to approach a case. Booth and his no-nonsense attitude towards scientists -- "squints" as he often calls them -- finds him preferring to get answers from witnesses and investigations, but working with Dr. Brennan he comes to see that the science behind the crime is often just as important as the witnesses.