The two forensic teams come back together under the leadership of Grissom and Catherine just in time to tackle three separate investigations: a murdered couple found in bed in a suspicious trailer explosion; a beautiful stripper discovered dead and dumped in the worst part of town; and two bodies found baked and decomposed after spending five days in the trunk of a car exposed to the hot Vegas sun, forcing the CSIs to ""wrap"" up the evidence and bring it back to the lab for further analysis.
Nick takes the lead on a case where in the house a family of four, three pools of blood are found. Nick thinks that the little girl may still be alive, but Sara is doubtful, thinking that Nick's recent near-death experience is affecting his judgement.
A 28 year-old single mother is found dead. Initially, it's believed to be a suicide, but Catherine determines she was murdered. Also, Ecklie summons Grissom to refute the testimony of an entomologist in a murder trial.
The team must investigate the death of a police officer who died during a shootout leaving hundreds of bullets on the crime scene. The case becomes complicated when it turns out that Sofia Curtis and Jim Brass were with the victim during the shootout. When it turns out the officer died from friendly fire, it is up to the team to find out who fired the fatal shot. Meanwhile, Sofia is wondering whether she fired the fatal shot or not. She decides to hide the fact that the officer stepped into her line of fire, afraid it will ruin her career.
Catherine and Brass investigate the case in which a man is found dead in a dumpster. It soon turns out the man had a serious food problem. The trail of his death soon leads to a hotdog-eating contest.Meanwhile, Nick and Sara investigate a not-so-amicable divorce with a bizarre twist. So bizarre it eventually lead to murder when both are found dead and it looks like the dog killed one of them.
The CSI's are called out to investigate the disappearance of a boy whose father died four years ago. Soon a couple is arrested at a convenience store with a boy matching the description of the missing kid. The only problem is they both claim it is their son. Both parents have exactly the same picture of the boy, with a scar on exactly the same place on his face. They hope a DNA-test could confirm who the real parents are, but when this information comes to light, it lead to another bizarre twist, possibly murder.
The CSI team investigates the murder of a man suffering from a congenital hypertrichosis, causing him to grow excessive body hair. Elements of the case suggest a connection with a belief in werewolves. The case leads to the victim's sister, who suffers from the same disease. Because of her condition, she'd been hiding from the world, but it turns out that she's hiding facts that are vital to solving the case.
The CSIs crash an elegant party for the city's crème of the crème to discover who killed a young man. The case gets a bit more personal for Catherine when her father, Sam Braun, is one of the suspects.
The CSIs become the focus of a reality TV series, which follows them while they investigate a serial rapist, who recently gained access to a woman's apartment by posing as a fireman. Also, Warrick's work on the late-shift is causing problems with his marriage to Tina.
When a student is arrested and tried for the murder of a popular high-school girl, the suspect's 12-year-old sister confesses to the crime. This results in the judge giving the prosecution 72 hours to re-examine the evidence before the jury delivers its verdict.
The team investigates the death of a psychic who "saw" her own death while performing a reading for two other women. Greg reveals a family secret to Grissom but Grissom believes that science will be what solves the case.
A wealthy defense attorney is killed at her son’s wedding but Nick’s car, containing all the collected evidence is stolen and the case is compromised. After discovering new evidence, the team suspects that someone from the wedding party may be responsible for the murder.
A high roller who spent the night with a woman he had just met is found dead on the loading dock of the casino where he was staying. The investigation reveals that the victim won $10,000 in a pool game and was an assistant to a respected movie producer.
A man accused of murdering his wife and co-workers leads the CSIs on a wild ride through a busy casino, eventually barricading himself and a hostage in a casino hotel room. The CSIs process the evidence from the crime scene to determine whether or not the man acted alone or had an accomplice. One of the CSIs eventually steps in as a hostage negotiator, putting himself in danger.
In the season finale, the CSIs wait by the bedside of one of their own when he's shot in the line of duty. One CSI faces a hard choice by having the power of attorney over their injured friend and colleague. Meanwhile, the team also investigates the strange way of life of one man when he is found decapitated by a train.