Gil Grissom is the supervisor of the graveyard shift of Las Vegas' elite crime scene investigators. Holly Gribbs, fresh out of the academy, joins the team. Jim Brass is head of the unit and is trying to scare Gribbs from CSI. Catherine Willows, mother of a young daughter, is the number two CSI on this shift. Warrick Brown and Nick Stokes are competing to solve their 100th case to earn a promotion to CSI 3. Grissom investigates a murder staged to look like a suicide with precious little evidence. Warrick and Catherine take the case of a drunk who breaks into the house where he had been staying and is shot to death. Nick talks to a man who picked up a woman who drugged and robbed him.

A man is killed after winning a fortune and then dumping his girlfriend. So, Grissom, Nick, and newcomer to the CSI team, Sara Sidel, investigate this one. Holly Gribbs is in the hospital and Warrick is up for suspension for leaving her at the crime scene by herself. Holly later dies in the hospital, but Grissom doesn't suspend Warrick.

Grissom, Nick, and Sara search for a kidnapped woman and find more than they expected. Catherine and Warrick investigate the hit and run death of a little girl.

Grissom and Catherine investigate when a leg is found severed from a body in a lake. They suspect the husband and boyfriend. Meanwhile Sara and Nick investigate a fraternity pledging gone terribly wrong.

Grissom and Warrick take the case of a young man who is found naked in the desert without an obvious cause of death. Sara gets to find out why the body of a woman who was buried last week is in a dumpster. Catherine and Nick investigate the killing of a school's dean by the school's founder.

Catherine violates department protocol when she takes the case of a rape accusation against her ex-husband. Warrick and Sara search for the missing bullet that will either exonerate or indict a cop for murder. Grissom and Nick investigate when a female skeleton is found under a house buried in cement.

When a teenager and her sister are the sole survivors of the gruesome murder of four members of one family in a quiet suburban neighborhood, Grissom and his entire team investigate the crime. What initially looks like a bizarre cult murder becomes more disturbing when they discover the motive behind the massacre.

Royce Harmon was murdered 3 months ago in a scene staged to look like a suicide. Now another murder has taken place. Whoever the killer is he has a thorough knowledge of forensics, he purposefully has left evidence, and has baffled Grissom and his team. Warrick and Nick investigate the case of a man who went over a cliff in his car and is now unconscious.

Grissom and his team investigate the death of a first class passenger on a flight to Las Vegas. The investigators are forced not only to examine the physical evidence, but also to interview all of the first class passengers to get their personal accounts of the incident.