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.

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.

A bomb goes off in an office building killing one and injuring many more. The chief suspect is a security guard who left minutes before the explosion and has knowledge in bomb making. Nick helps his prostitute friend again. After giving in to his passion, she is found dead the next morning. Naturally, Nick is a suspect and to make it worse, Ecklie has the case.

A body is found in a pottery store in what's apparently a robbery that was interrupted. Fingerprints at the scene seem to match a twenty year old kidnapping case. Sara and Warrick look into a case where a woman burned to death in her home. The woman was burned to an ash but only the chair she was in was burned, the rest of the house is fine. Sara believes they have a case of spontaneous combustion.