Gil Grissom, the supervisor of the graveyard shift, along with his unit, including Captain Jim Brass; Holly Gibbs, the newest investigator; Catherine Willows, a single mother and the number two CSI; and Warrick Brown, a young investigator competing with fellow CSI, Nick Stokes, for a promotion. Grissom investigates the case of a murder set up to look like a suicide, but finds it hard when he only a few pieces of evidence are found. Warrick and Catherine are assigned to the case of drunk man shot to death. Meanwhile, Nick talks to a man who picked up a woman who once drugged than robbed him.

After the Gribbs shooting, Detective Brass is reassigned to homicide, leaving Grissom as head of the CSI unit. To investigate the shooting, Grissom brings in Sara Sidel, an investigator from San Francisco, and assigns her to the case, much to the disgust of Catherine, who wanted the case for herself. Meanwhile, Grissom and Nick investigate the suicide of a man who recently won a large jackpot.

When a woman goes missing, Grissom, Nick and Sara are assigned to her case. But in their search for her, they come across more than they had expected. Meanwhile, Catherine and Warrick investigate the death of a girl who was killed in a hit and run.

Grissom and Catherine team up when a severed leg is found that belongs to a body recovered from a lake. They suspect that the husband and the boyfriend are to blame, but who will the evidence point to? Meanwhile, Sara and Nick investigate a fraternity pledging ceremony that turned deadly.

Grissom and Warrick investigate the death of a young man who is found naked, but the cause of death isn't obvious to the duo. Sara is sent to investigate when the body of a woman who was buried in a cemetery the week before turns up in a dumpster. Catherine and Nick explore the murder of a school's dean committed by the school's founder.

Despite department procedure, Catherine takes the case of an rape that may have been committed by her ex-husband. Warrick and Sara hunt for a missing bullet that will be able to exonerate or indict a cop in a murder investigation. Meanwhile, Grissom and Nick are sent to investigate when the remains of a female are found buried under a house.

The team is sent to the scene when a teenager and her younger sister are the only survivors of the brutal murders of their four other family members. The team believes that the murders were bizarre cult murders, but once they stumble across a motive, the murders become increasingly disturbing.

Three months ago, Royce Harmon was murdered and his killer staged the scene to make it appear to be a suicide. Now another another murder has been committed, and the killers knowledge of forensics has left Grissom and his crew bewildered. Meanwhile, Warrick and Nick investigate when a man drives over a cliff in his car and is now unconscious.

When a passenger is murdered on a flight to Las Vegas, Grissom and the team have to find the killer. To do so, the team must examine the physical evidence they collect as well as interview each of the first class passengers to get their story of what happened.

A body covered in bugs is found abandoned in the desert, leaving Grissom and Sara to figure out where it came from and who killed the victim. Warrick and Catherine investigate the theft of valuable pieces of art while Nick is assigned to uncover the truth about why a missing woman's car is found at a bus station. Later, Warrick is suspended when he is suspected of gambling while on duty.

A woman is kidnapped from a supermarket. there, Grissom finds writing on a bathroom stall that claims that five other women have been killed. After being caught on duty in a casino, Warrick is paired up with Sara, who is reluctant to do so. Together, they work on a robbery-murder case. Meanwhile, Nick is asked for help by his prostitute friend after she gets into a fight with hotel security.

A man seeks out Grissom to help prove his innocence when he is convicted of arson and the murder of his wife and child. Catherine and Nick are sent into the underground world of gambling after a teenager is murdered.

When a bomb explodes in an office building, resulting in the death of one and injuring several others, the CSIs are sent to investigate. They soon suspect a security guard who was seen leaving only minutes before the explosion and has the knowledge required to make a bomb. Meanwhile, Nick helps his prostitute friend again, but when she is found dead the next morning, Nick becomes the main suspect.

A human bone is discovered in the desert, forcing Grissom and Catherine to search miles of desert for traces of the rest of the body. Meanwhile, Warrick and Sara investigate the death of a male stripper and soon trace the death to a wedding party that may have gotten out of hand the night before the ceremony.

A woman winds up dead at a classy fundraiser and the CSIs are sent to investigate. The owner of the house is out of town, turning the suspicion to the couple house-sitting for the owner. Meanwhile, Warrick investigates a murder committed in a glass elevator. After some investigation, Warrick discovers that the victim had a professional hit put out on him.

A woman kidnapped from a parking garage, then raped, beaten and shot. The longer Sara works on the case, the more attached to the victim she becomes. Catherine and Warrick are given evidence from an upcoming murder trial when the current CSI on the case quits. Meanwhile, Eddie, Catherine's ex-husband, has taken out a second mortgage without telling her.

A body is found in a pottery store and the scene looks like a robbery-homicide. Fingerprints at the store link the death to a twenty year old kidnapping case. Sara and Warrick team up to investigate the case of a woman who burned to death inside of her house. After some investigation, Sara is led to believe that they have a case of spontaneous combustion.

A couple celebrating their anniversary are killed in front of a restaurant and their car is stolen. The CSIs run into trouble when it begins to rain and the crime scene is compromised. Soon the car is uncovered and evidence is collected from the car. Meanwhile, Catherine investigates the collapse of a residence that killed three women.

The CSIs investigate the kidnapping of an infant from a wealthy family. After some investigation, the CSIs begin to suspect that the parents had more to do with the disappearance then they're letting on.

While driving, two women run over a deaf man, but he was already dead when they hit him. Grissom is sent to uncover who killed him, but only finds dead ends when the deaf man's school refuses to help. Catherine and Nick investigate what appears to be a professional hit that resulted in five murders at a coffee shop.

Grissom, Nick, and Warrick investigate the death of a jogger who was killed by a wild animal near a park. Things take a mysterious turn when they find that the jogger's liver had been removed after he had died. Meanwhile, Sara and Catherine investigate the death of a young girl at a carnival.

It's evaluation day, but the Grissom's evaluations take a back seat when a head, severed from its body, is found in the trunk of a car. Meanwhile, Sara and Nick investigate when a body turns up in the desert, and it's missing its head. Warrick is sent to the juvenile detention center after a teen is murdered. The only witness to the death is Warrick's young friend, James.

The team is sent to investigate murders committed by a signature killer. However, leads are hard to come by since the killer obviously have knowledge of forensics and has left behind no evidence. With the investigation going no where, the FBI are called out, angering Grissom.