"Once hope is gone, dying's just a formality."As gritty crime dramas, it's not surprising the series that consist of the CSI Verse have quite a few monstrous villains.
—"John Smith", Cold Case, "The Road"
- Mandy and Cameron Klinefeld from season 4's "Assume Nothing" put the "unholy" back in Unholy Matrimony. A married couple united by a shared sexual fetish for rape and murder, the pair operate by abducting other husbands and wives, sexually torturing the women while making the men watch, with the ultimate goal of forcing them to Mercy Kill the women they love. They promise the husbands they can go free if they do this, but they're lying.
- Season 12 Arc Villain Laura Gabriel is a ruthless arms smuggler and Big Bad Friend to Catherine Willows. Playing a meek and submissive wife to her sleazy private military firm head husband Mark, she uses this false personality to deflect blame off her and onto him as she funnels his company's weapons to The Mafia and The Cartels. When the investigation starts getting too close to the truth, she hires employees of the company to murder her own lawyer and all of his staff; following this, she kills the assassins and burns their bodies beyond recognition in order to fake her own death and that of her right-hand man. She intended for an enraged Catherine to summarily execute her husband, and placed a contract on Catherine herself to clean up the last remaining loose end, not caring for her old friend in the slightest.
- Stewart Otis, first appearing in season 1's "Broken", is a pedophilic Serial Rapist who targeted little girls around the ages of five to eight years. While acting as an authority figure, he would kidnap the girls to take to his home for him to rape and strangle to death before burying the bodies in is backyard. He has done this to eight little girls and only lamenting on his latest victim, Ruthie, because she died too quickly before he got a chance to "play" with her. He later appears in the season's finale "Body Count", where he escaped prison with the help of two fellow inmates, Hank Kerner and Randall Kaye. He then returns the latter's favor by kidnapping his daughter, Emma, taking her to a cabin where he not only raped her, but force her to partake in a film taunting Horatio Caine, the person who arrested him. He then tries to kill her note before trying to find her cousin, Robyn, hoping to do the same thing to her.
- Henry Darius, from a CSI: Miami-CSI: New York crossover, is a Serial Killer-turned-spree killer known for shooting his victims in the head. As a child born from a mistress of a wealthy family, he always felt jealous that his half-sisters got more attention than he did, and as a result, became a murderer, with his first three victims looking like his sisters. First appearing in the season 4 Miami episode "Felony Flight", he causes a plane crash that kills two pilots and one U.S. Marshal. He then steals the marshal's gun and uses it to kill four college students and steal their car. He then travels to Miami University where he would kill two more college students after they told him about his half-sister, Alexa, and her whereabouts. He then goes to her location and kidnap her before shooting a man for his car and heading to New York City. When he arrives there in the season 2 NY episode "Manhattan Manhunt", he murders Alexa along with six college students, before heading off to kill his second half-sister Sarah. A narcissistic sociopath, with a violently-low impulse control, poor Freudian Excuse, and 20+ body count to boot, Henry Darius was among the worst that both CSI teams from Miami and New York had ever had to face.
- Josh Freely from season 1's "Fly Away" is a brutal pedophile that uses his position, as a social worker working with emotionally unstable parents, to find new victims. Freely piles emotional abuse onto the parents, making them feel as though they're worthless, so they surrender their kids to him, and if that doesn't work, he's more than happy to fudge his own records so his superiors order the children removed. His abuse eventually reaches the point that one such mother attempts to kill herself and her daughter rather than let Freely take her.
- The season 1 finale, "Lovers' Lane, " brings us Jim Larkin, a slovenly glutton and serial rapist. Too lazy to even abduct victims himself, he instead badgers his abused and weak-willed son to do so for him, usually unattractive teenage girls he pretends to befriend. His assaults are brutal, reaching the point at which he murders one of his victims simply for calling him "disgusting."
- Roger Mulvaney, of season 3's "A Perfect Day" ruthlessly beats his wife and two daughters and uses his position as a police officer to get away with the abuse. Once his wife decides to leave him for another man he resolves that if he can't have them, nobody could. He kidnaps the three of them and makes his wife watch as he throws one of the girls from a tall bridge.
- The unnamed killer going by the alias "John Smith" from season 5's "The Road" is the most horrific Serial Killer seen on the show. Disturbed since childhood, he described the sight of watching a woman drown while doing nothing to save her as the most beautiful thing he'd ever seen, and dedicated his adult life to replicating that "beauty." Abducting women who were perfectly happy with their lives, Smith brought them to special cellars where he sealed them off, watching as they went insane from isolation before finally leaving them there to starve.
- Rayanne Leland from season 5's "Spiders" is a sugary-sweet stay-at-home mom who also happens to run a Neo-Nazi coven out of her basement. When her son Truitt murders a Hispanic woman, Truitt's girlfriend, Tamyra, turns to Rayanne for help, only to find to her horror that Rayanne wholeheartedly supports her son's actions, and calmly tells Tamyra that all Hispanics should be exterminated, her warm, loving smile never leaving her face. When Tamyra threatens to go to the police, Rayanne browbeats the most insecure and sympathetic member of the coven, Elliot, into murdering her.
- Daniel Patterson from season 5's "Slipping" is the ultimate gaslighter. Insanely jealous of his wife's skill at poetry, he hatched a plan to both steal her work for his own and get rid of her. With the aid of his slavishly devoted housekeeper, he did everything in his power to drive his wife insane and ultimately to suicide, maintaining a façade of a caring husband all the while. When he failed to break her, he murdered her himself. To prevent his stepdaughter from knowing the truth he sent her to a notoriously harsh boarding school, believing his story that her mother committed suicide for 45 years.
- Season 3's finale and season 4's premiere had Emil Dornvald, a mercenary working for an African dictator. The missing person of the week is in love with a rebel opposing said dictator and knew where he and his friends were holed up. Dornvald cold-bloodedly murders the pregnant teenager she's been mentoring and is very fond of, sends her a picture on the girl's phone, and offers to stop killing her loved ones if she just tells him where the men are.
- Season 6's premiere had a conman preying on families who had adopted children from Africa; he'd claim to be the kid's birth father and guilt the parents into surrendering the kids to him, whereupon he'd take them and sell them on the black market. He also manipulated a Sudanese war orphan into helping him by claiming that he was only stealing the children to get them back to their birth parents, the young man having lost his own mother to militants. When the orphan finds out he's been had, he brutally stabs the guy to death and the FBI quite understandably decide to look the other way.
- Level 26: Dark Origins: This digital novel, by CSI creator Anthony Zuiker, features Sqweegel, real name unknown, the most prolific serial killer in history within the CSI world. Sqweegel is known for incredible preparation and his seeming randomness. Once he locks in on a victim, Sqweegel proceeds to murder them, often after torturing and raping them, with gender being irrelevant to his tastes. Sqweegel initiates the book's plot by sending in a homemade snuff film to the authorities, and proceeds to kidnap three teenagers who tried to illegally tried to buy beer before raping them with himself, a mop handle and a baseball bat. He burns six priests alive and attempts to torture the widows of 9/11 firefighters to death. His true enemy is the investigator Steven Dark, whose foster family was murdered by Sqweegel once Dark came close to catching him years ago. To “punish” Dark for cheating on his wife Sibby, Sqweegel had raped Sibby, possibly conceiving a child which Sqweegel plans to kill, along with raping and killing Sibby. With a body count numbering in the high hundreds and the belief he is an instrument of divine retribution, Sqweegel remains the most terrifying enemy of Dark's career, and is the only known serial killer to receive the classification Level 26 to designate a monster that was previously beyond human comprehension.