A taxi driver accidentally runs over a teenage boy. He is later brutally beaten by a gang who thinks he is running away. Grissom and Sara works on the case and finds that the boy was dead prior to being hit from a stab wound.

The sheriff of desolate town Jackpot calls in CSI for assistance after a severed head is found. The sheriff proves rather more cynical than helpful towards Grissom, unlike the veterinarian-coroner. The rest of the corpse is found buried to the shoulders alive, a Native American torture technique. Grissom triumphs over sabotage and works out the local reports and relevant secrets.

Because Warrick naively assumed simple uniformed cop Hal Watson would have arranged a search warrant, the crucial weapon in the rape and murder trial on a neighbor against Michael Fife is dismissed as evidence in court. A.D.A. Jeffrey Sinclair can only get a 24 hours delay to present new evidence to build the case again. Nick brilliantly smooths emotional waywardness from Sarah and Warrick. New clues expected to reconstruct the case against Fife actually indicate he's probably innocent. An alternative culprit must be found, starting from Fife's car where the bloody knife was planted.

When the body of Vanessa Keaton is found drowned in water fountain in a gated community and hit on the forehead, Grissom, Sara, Greg and Capt. Brass assume the investigation. Soon they learn that Vanessa was in a swingers' party, but the water in her lung is not from the fountain. They interview the owners of the house and guests and collect the water in the swimming pools to see if any of them match the water in the lungs of Vanessa. Mia examines the DNAs in the several condoms in the garbage bin. Meanwhile, Warrick, Nick and Det. Chris Cavaliere investigate the murder Mr. Basengi, the landlord of a video arcade. They find an eviction notice to the tenants are Melissa Poolie and Charlie Pinscher that become prime suspects. They visit Charlie that tells that Melissa was his girlfriend and left him with the rent. They learn from Marty Gleason, a member of the crime scene cleanup, that the place has a decomposed smell and Warrick and Nick find the body of Melissa hidden in a game and Charlie is brought back to the interrogation room.

When the flight attendant Martha Krell is found dead and raped in her hotel room, Grissom, Greg, Sara and Capt. Brass investigate the case. They note that there is no luggage in the room that was cleaned and sanitized without any evidence. Ecklie tells Sara that he had a similar case five years ago, with the flight attendant Sue Stein. Sara notes that the present technology is able to retrieve the fingerprint from the previous case. Meanwhile, Catherine, Nick, Warrick and Det. Chris Cavaliere investigate the case of the death of the twelve-year-old Ty Hawkins, who has been beaten to death on his bed while sleeping. His fourteen-year-old brother Matt becomes the prime suspect to Det. Cavaliere and when Matt confesses the murder of his brother, Nick questions the way Det. Cavaliere conducted the interrogation. The CSI team proceeds the investigation and finds two other suspects: Ty's father Martin and the homeless Walter. Who might be the murderer?

When a Hummer in the wrong way runs over an old Fiero, Grissom meets Capt. Brass to investigate the scene. He learns that the Hummer's driver has fled and the Fiero's driver is alive in the hospital. At a car convention, when the host Mr. Daluca opens the curtains to show the latest RV model to the audience, there is a dead woman. Warrick and Det. Louis Vartann learn that the victim is the twenty-nine-year-old model Lisa Schumacher. Dr. Robbins tells Catherine that Lisa was asphyxiated and she had sex before her death. Daluca becomes their prime suspect. Meanwhile, the model Gwen that is working at the convention, goes to the house of her personal trainer Paul Charles to workout and sees him dead through the window. Greg and Sara investigate the crime scene while Dr. Robbins carries out the autopsy. When he sees a black substance in his eye, Hazmat takes Sara and Greg to the decontamination shower. When the body of a boy is found on a bus stop bench covered by a blanket in front of a laundromat, Nick investigates the case. Dr. Robbins tells Nick that the cause of death was asphyxia from heat damage. They identify the victim is Chase Ryan and Nick tries to understand what might have happened to the boy.

CSI team goes back to investigate crime scenes as a team, re-united together after the traumatic experience in season five finale. Nick's kidnap case audio tape arrives at the laboratory.

When one Trenton cop is murdered in Las Vegas, a second threatens to expose Keppler's past if he doesn't make the case and the evidence go away.

A death in a drive-by limo shooting and the dragging death of a young woman turn out to be related crimes, and Greg discovers that the brother of the young man he ran over may have been involved.

After an unsuccessful attempt on Lady Heather's life, Sara discovers Gil's prior relationship with her. Meanwhile, Nick investigates the death of a woman apparently hit by a taxicab.

The miniature killer is ready to strike again, and Sara will be the next victim. Will CSI stop her in time?

The murder of a co-ed leads to the investigation of a brother and sister who were involved in another murder case from Sara's past, and the case drives Sara over the edge.