The CSI team is summoned to investigate the death of the first-class passenger Tony Candlewell in twelve hours because of a jurisdiction problem. Candlewell has contradictory evidences of aggression and defense, and the first class passengers are secluded in the airport and interviewed. But Catherine and Brass note that they are hiding information. Meanwhile, in the autopsy, the coroner learns that Candlewell had undiagnosed encephalitis, the reason of his berserk behavior. When they find shoe prints on the back of his jacket, the passengers Lou Everitt, Max Valdez, and Dr. Kiera Behrle .are considered prime suspects. The team interviews the blind Mr. Cash that was near the incident and using dummies later, they represent the statements and come to a conclusion of the case.

When a young woman riding a horse finds a body of a woman inside a pipe in a construction site, Grissom and his team investigate the murder. Soon they find another woman's body and coroner Dr. Albert 'Al' Robbins notes that the women are very different despite being sisters. Their further investigation indicate the Donna Marks was a reclusive woman, maybe agoraphobic, while Joan Marks had a different behavior. Meanwhile, Catherine and Nick investigate the murder of the hunter James Jasper in the woods. James was an insurance broker and an experienced hunter, but was not wearing the safety vest. Catherine, Nick and Detective Vega learn that Jasper and his wife Linda had lost their jobs. When they find a one-million dollar life insurance on behalf of Linda, his wife becomes their prime suspect.

The discovery of a dead man in the wilderness in a fursuit leads to an investigation at the goings-on at a furry convention.

Julie Waters, a dancer, has been missing for 6 days. A suspect, Howard Delhomme, calls the police and turns himself in. He refuses to talk to anyone but Catherine. Sarah and Nick want to work on this case because they see it as a career-making step. Grissom, to their anger and disappointment, hands the rein over to Catherine. Despite their initial antagonism, they all worked together to find the young girl.

The body of a young gambler is left at a neon graveyard. He died from two gunshots to the back of his head. Prior to his death, he won a lot of money from one of Sam Braun's casinos. This makes Grissom remove Catherine from the case.

When Linley Parker survives a rape attack, the CSI team investigates the case. Linley identify her aggressor Dr. Todd Coombs, but their DNA do not match and Todd is released despite the identification. His brothers become the suspects based on the DNA results, but they do not find the guilty. When Linley is murdered, the CSI team discovers new genetic condition in the case.