Following the cliffhanger of "Vacation Getaway", Lindsay Monroe Messer kills Shane Casey. Five months later she is awarded a Combat Cross. She and her team return to the crime lab where Stella Bonasera's replacement, Jo Danville has found the body of Sarah Nelson, a secretary in an architect's office on the floor below the crime lab. They determine she was killed by a pair of scissors. Later, they hear of a second victim from the office, Theodore Westwick, who survived an attack. After finding a dropped pair of scissors, the CSIs match the fingerprints to a high-end thief. When Danny and Flack catch him, he claims that he broke into the office and witnessed Westwick murder Nelson, and later defended himself when Westwick attempted to kill him, too. Danville and Hawkes prove the burglars claim. When Mac's team arrives to arrest Westwick he pulls a gun to make Mac and Flack shoot him.

A beautiful young woman is strangled to death while she is having an online chat with Adam Ross. The victim is 20-year-old Sass Dumonde (Amra Silajdžić), a French music student, who is actually studying in New York City. At the crime scene, the team finds that the murderer took one of her laptops, which belonged to Draga Financial, an investment firm under investigation by the FBI. Hawkes determines the face behind the mask of the killer is an employee of the firm. When Mac arrives at his office he finds him gone and targeting Adam. When the murderer tries to kill Adam, Adam is able to subdue him while the police arrive. In the end, Mac, having learned Adam previously hacked into Draga's system against his permission, puts him on a three-day suspension.

A married couple are found beaten in their home, with the husband dead and wife barely alive. The woman identifies her son, Billy Travers, as the attacker. However, there are a series of complications in the case. First, the mother is suffering from amnesia, and later does not recall who attacked her. Next, a convict facing a life sentence who broke out confesses to the crime; is this a ploy, or is the real attacker still on the loose?

Members of El Puño, a Puerto Rican gang, are found murdered only days after the release of its founder, Luther Devarro (Edward James Olmos), whom Mac arrested for murder several years earlier. Believing a rival gang is responsible, Mac asks Devarro for help in solving the murders, concerned that the NYPD may have a gang war on their hands.

Danny's former partner is involved in a jewel robbery at the home of a powerful defense attorney.

When a badly decomposed body is found in an abandoned car on a rooftop, Mac and his team must go up against a killer who is using the parents of his victim to manipulate crime scenes.

When a rooftop sniper with exploding bullets starts killing, Mac's duty to protect and serve conflicts with his superior's orders concerning civilians' right-to-know. Mac has a history with the main suspect. Sid is injured during an autopsy.

A park runner tries to escape from her killer. When her body is discovered an autopsy reveals that she had literally been scared to death. Soon afterward, a second victim who could be connected to the case is discovered, who turns out to be Chief Carver's missing sister.

Mac continues to investigate Chief Carver's sister's death, which leads him to suspect the chief himself.

A department store manager is found dead inside his store's holiday window display. Several employees had motive.

A man dressed in a full clown costume shoots a bakery owner. The case connects to an old one of Flack's. Jo's ex-husband shows up.

A Catalan club promoter is killed and Mac battles with a detective from Barcelona to solve the case. Things get personal when the relationship between the detective and victim is revealed and Mac wonders why the detective believes the case is a homicide, despite evidence pointing to suicide.

When a tractor-trailer is found at the bottom of the Hudson River carrying exclusive party guests, Mac and his team must solve the mystery.

When a charming and suave hitman (Ne-Yo) goes loose in the city, a hidden conspiracy involving counterfeit prescription drugs is uncovered.

When a serial rapist is found murdered in the same manner as his victims, the CSIs weigh a feeling of justice against their sense of duty to pursue the killer.

The CSIs investigate the murder of a conspiracy-obsessed woman whose ramblings seem to contain some truth.

The CSIs dive into a highly competitive world to catch a killer who murdered a popular girl in a Manhattan private school. However, the school is worse than they think it is.

When her adopted daughter becomes the key witness in a murder investigation, Jo faces a conflict between her personal and professional lives.

Mac and his team investigate a murder at a SoHo food festival where Hawkes and his girlfriend are two of many witnesses.

During a murder investigation the team stumbles on a missing person case. An ex-convict seems to be stalking Mac and it ties to his old partner (Peter Fonda).

The crime lab is attacked. Danny and Mac are investigated by Internal Affairs after killing a suspect. Mac's old partner and the ex-con reveal what happened years earlier.

After a near-death experience Mac returns to his final unsolved case, a bodega robbery in 2002. New evidence suggests a young girl was kidnapped during the crime, so Mac and the team launch a country-wide manhunt to find her. She is reunited with her mother, and Mac tells Jo he believes he has done his share of good.