When April Perez reports that her thirteen-year-old Alicia Perez has been kidnapped by an Afro-American man driving an old Buick, the CSI team investigate the scene and an Amber Alert is issued. Capt. Brass interviews the parents Sybil and Carlos and he learns that April had drug problem. Meanwhile, Grissom and Sara look through Alicia's room and Sara learns from Alicia's brother Daniel that his sister was in love with her schoolmate Jimmy Jones. When they meet Jimmy, the boy tells them that Alicia was upset since she would have to donate her kidney to Daniel and she liked to play soccer. When they find the body of Alicia dumped on the road, they make news discoveries about the case.

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 a group of fraternity members find a spot covered by maggots, Grissom investigates the scene and believes a student is providing the flesh to the maggots. Based on the uniform size of the bones and woods, Nick and Grissom believe a mulching machine was used to discard the body, and soon they find evidence in the machine. Based on a fingernail found in a garbage bag, Catherine concludes that the Blue Painter Killer is back. Now the entire team is working on the case.

While driving her convertible at high-speed in the highway, a woman is stopped by a patrolman. Catherine and Grissom arrive later to the highway where the woman was found with slit throat and slashed genitals in her car. They also find a camcorder with no tape on the floor. The entire team investigate the case and Warrick and Sara find documents in the car, showing that the victim is Wendy Garner and the car's registration and the driver's license in the name of Walter Clancy. When Dr. Robbins finds a prostate in the victim, the team learns that she was a transsexual, and soon concludes that Wendy and Walter were the same person. When Grissom and Brass investigate Wendy's fiancé Aaron Laner, they learn that he does not know that Wendy was a transsexual. The team also interview her fellow dancers and learn that Dr. Mercer is the responsible for most of the transsexuals' operation. However, the doctor tells Catherine and Warrick that he refused to operate Wendy since she wanted to jump steps of the procedure required by the law. Now they are looking for the surgeon that might have operated Wendy.

While giving his testimony in a retrial, Grissom sees fingerprints on a matchbox that he does not recall. The victim Max Larson was found dead I his hardware store hit by a wrench. He requests a recess to the DA and reopens the investigation of the case. He follows the protocol and assigns Catherine, Warrick and Nick to investigate the case again and why they have missed the fingerprint in their investigation. Ecklie asks Sofia to investigate Grissom's cases and begins a witch hunt in the laboratory. Meanwhile, Sara, Greg and Det. Louis Vartann investigate the case of a John Doe, who died after shooting his own leg. When they succeed to find the register of the gun, they find clue of another case.

Grissom, Sofia and Greg investigate a gang shooting with two victims. Out of the blue, Greg finds the body of a young boy dumped in a trash bin. Sara and David Phillips join the investigation. Dr. Robbins notes in the autopsy that the boy was around five years old, was abused with several recent fractures and died of starvation. A further investigation identifies the boy as Devon Malton and Sara and Capt. Brass visit the foster home where he lived with Lorna Tenney. Meanwhile, Catherine, Nick, Warrick and Det. Louis Vartann investigate the case of the prisoner Samuel Mendez that was beaten up in a riot in a cell and now is brain dead. Warrick sees a gun in the cell that was under Samuels body. Lt. Arthur Chen that is the responsible for the prisoners has an argument with Warrick when he comments about a sloppy police search and abuse of force. Soon they learn that Samuel Mendez is not the wanted criminal but an innocent namesake.

When the wealthy casino owner Bruce Eiger is found dead on the front steps of his mansion, Ecklie assigns the entire team to the case. They investigate whether Bruce has jumped, felt or was pushed off the second floor. In the autopsy, Dr. Robbins finds that Bruce was sodomite, with repeated insertions into his rectum. When they find a secret compartment in Bruce's mansion, they are forced to understand the bizarre world of Infantilism.

Catherine, Warrick and Nick investigate a shotgun killing in the desert. What they come across however is a beaver dam full of money. When they subsequently learn that the victim worked at setting the spread for sports betting, they think he may have a betting scam of some sort. Grissom, Sara and Greg investigate a death in a hotel where someone is found suffocated in his bed. He was staying in a hotel hosting a convention for overweight people and was quite popular with the ladies.

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?

A man is observing the sky with a telescope when, out of the blue, he is burned by a blaze. Grissom and Sara arrive to investigate the scene when Grissom finds a woman still live but completely burned. They believe it was arson and Sara uses the fingerprint in a broken bottle of cheap vodka to identify the truck driver Patrick Bromley. Meanwhile, Catherine, Warrick, Nick and Capt. Brass investigate the murder of the Stewart family, where the parents were shot and their five-year-old daughter Dani drowned in the swimming pull. Nick believes in the murder-suicide theory while processing the evidences. When they learn that the DNA in both cases belongs to the burned woman, they realize that the cases are the same.

After a tough day at the work, Catherine invites Warrick and Nick to drink in a bar. She goes alone and meets Adam Novak, a stranger that fives his phone number in a matchbook. He offers to go to her car with her, they kiss each other and Adam turns brutal when she does not want to have sex with him. She hits her head on the door of the car and goes home. While sleeping, Catherine gets a call from Grissom and heads to the crime scene, where Alice Granger is found dead with a shot in her head. When Det. Vartann find her car nearby the bar where Catherine was, she goes with him to investigate. When she finds a matchbook in the belongings of Alice with a phone number, she heads home to find Adam's matchbook, but it has been thrown in the garbage. Their further investigation indicates that her ex-boyfriend, Jeff Simon, might be the killer, but he had a strong alibi. Catherine tries to tell to Grissom about her possible involvement in the case, but he does not give much attention to her. But when a second victim is found with the same M.O., they realize that the killer might be the same.

When the university students Paula Levine and Trip Wilmont are found dead on the floor after having sex in Trip's dormitory room, Grissom, Sara, Greg and Capt. Brass investigate the case. Grissom leaves the case since he has to go to the court and Sara and Greg use the monoxide carbon detector to look for a source, but they do not find any monoxide carbon in the room. Meanwhile, Brass talks to his next-door neighbor Zack Capola, who says that Trip and him were just mates, not friend. Sara and Greg proceed the investigation. Meanwhile, Catherine, Warrick and Nick join to David Phillip in the middle of a crop circle to investigate the death of a man. In the autopsy, they learn that the victim has urinated in his underwear. When the CSI team locates the owner of the helicopter that was in that area, they learn what has happened to Kevin Staniland. Meanwhile, Det. Louis Vartann finds that no investigator is available and Conrad Ecklie is forced to go with him to the Tangiers since there is a dead body needing to be processed. They learn that the victim is James Billmeyer from New Jersey and Ecklie requests the shoes of the woman that found the body since she stepped on the blood. When James' body vanishes from the morgue there is a further investigation.

With its desperate attempt to ransom Nick's release failed by their enemy's fanatical revenge, the CSI team must use all their investigative talents to find Nick, whose perilous situation is becoming all the more horrific by the minute.