Season four begins all the way in England, with Booth speaking at Scotland Yard and Brennan guest-lecturing at the prestigious Oxford University. Knowing of Booth and Brennan's expertise in their respective fields, local officials ask for their help with a high-profile murder investigation that involves a British heiress.

With the case of the murdered heiress solved, Booth and Brennan prepare to head back home, but are shocked to learn of another murder - and this time it's someone they know. Meanwhile, with Birimbau unexpectedly coming back into Angela's life, things get complicated between her and Hodgins.

When newlyweds encounter a corpse while bungee-jumping off of a bridge, Brennan and Booth are sent to investigate. After determine the cause of death was not suicide, the team at the Jeffersonian discover an unknown substance coming from the body. This sends the lab into lockdown and have only 24 hours to uncover the murderer before the body disintegrates.

Booth and Brennan are sent to investigate when human remains are found during a photo shoot. When the team uncovers a meteorite in the victim's ear, they are led to the Collar Institute of Science in D.C.

When it is discovered that a stage prop used by a Norwegian death metal band is in fact a real human skeleton, the remains are sent to the Jeffersonian when authorities determine the victim was an American citizen.

When a Jeffersonian coworker dies of heart failure, the entire team goes to the wake where, upon viewing the body, Brennan realizes the death was no accident.

Booth's detective friend from Tokyo, Ken Nakamura, calls him when his sister, Sachi, goes missing while in Washington, D.C. With Brennan, Booth investigates her disappearance.

When a human body is found inside the strung up Otter mascot uniform of a rival school, Brennan and Booth investigate whether the body inside the costume was dead beforehand, or killed during a Middlesex University bonfire event. The body is identified as Jimmy “Beaver” Bouvier, a fraternity brother at Middlesex University. When Brennan and Booth question his fraternity brothers, they learn that Beaver had a money-making operation on the side and was making a killing of his own. Meanwhile, Booth offers to help his brother Jared find a new job after being dishonorably discharged from the Navy.

The team is on the case when human remains are found inside a barrel of wine during a wine tasting. When the victim turns out to be a wine critic whose scathing reviews were capable of sending a vineyard to its ruin, everyone from the winery's owner to the victim's own wife becomes a suspect.

In the season finale, a dead body is found at a club called "The Lab." The team has to do some unexpected and unusual things that have to do with this club. Brennan and Booth may become a couple.