"You can kill a man but you can't kill what he stands for. Not unless you first break his spirit. That's a beautiful thing to see."The X-Files was a nine-season Long Runner, and monsters were the show's thing. Some of these were genetic mutants who acted on predatory instincts and followed their biological needs. However, several of them crossed into the Complete Monster territory. Often these cases were surprisingly light on the paranormal stuff, making them fairly mundane and all the more frightening.
—The Cigarette Smoking Man, "The Beginning"
- The Cigarette Smoking Man, also known as the Cancer Man, is Agent Mulder and Agent Scully's main antagonist, the villain of the Myth Arc, and the only Complete Monster who's not a Monster of the Week. He's associated with the grand government conspiracy Mulder and Scully are trying to uncover. While some of the conspirators are Well Intentioned Extremists, Cancer Man doesn't fit the bill. Whenever it would appear that he showed compassion or altruism, he in fact tried to manipulate people or played evil tricks on them. He had numerous means to neutralize his opponents, but he often chose especially cruel ways. For instance, he tried to burn Mulder alive and let Scully be abducted and experimented on, which gave her cancer and made her infertile. He had his ex-wife and mother of his son turned into an alien-human hybrid. He attempted to murder his own son in cold blood; said son survived, and Cigarette Smoking Man had him experimented on in unspeakable ways. He did save the Agents' lives a couple of times, or at least he didn't interfere with their attempts of saving each other, but he admitted he did it because it's satisfying to see their spirits crushed. Although he claims he wants to atone in "En Ami", it's clear doesn't want it enough to actually change and he never feels guilty.
- Cecil L'Ively from season 1's "Fire" is a pyromaniac who can ignite things with his mind and who himself cannot be hurt by fire at all. He's a creepy stalker and pursues women in powerful positions, burning their husbands and other family members, including children, to death. He seems to genuinely enjoy torturing people and shows no remorse.
- Donald "Donnie" Pfaster from season 2's "Irresistible" and season 7's "Orison" is a necrophiliac who collects hair and fingers of his female victims after he's done with them. His fetish escalates into him becoming a Serial Killer. He has some kind of twisted, sick affection for his victims which is utterly scary. He's a horribly menacing killer who shows no regrets for his deeds, looking surprised when he's caught, as if it was his right to treat people as he pleases.
- Phyllis Paddock from season 2's "Die Hand Die Verletzt" is a fake substitute teacher who may or may not be the demon Azazel. Her first onscreen appearance (albeit not fully seen) involves her lifting a teenage boy into the air by his neck before brutally murdering him, tearing out his eyes and ripping out his heart, all because he was unfortunate enough to have accidentally summoned her. Later, she caused the death of a young girl by taking control of her and forcing her to slit her own wrists, only because she was the stepdaughter of the leader of a coven whose belief in the demon had lapsed. She then caused said leader to be gruesomely devoured by a snake familiar, and the other three members of the coven to kill themselves. The only reason for her murders was that the coven had become lax in the practice of their religion, and had stopped providing Azazel with sacrifices.
- Colonel Jacob Wharton from season 2's "Fresh Bones" is a sociopath who tortures people from Haiti who are held at an immigrant camp he's in charge of. It's revealed that he's responsible for several deaths: a small boy, a Haitian prisoner who knew voodoo and several of his soldiers that tried to stop him. He thought it's good to kill emigrants, rather than sending them back home.
- Dr. Jack Franklyn (real name: Dr. Clifford Cox) from season 4's "Sanguinarium" is a demonic doctor and a narcissistic warlock who makes human sacrifices by taking over the minds of various surgeons and having them kill patients in horrific ways (draining a patient's blood via liposuction, nearly cutting a patient's head off with a laser, and melting a patient's face off) so that he can retain his youth and looks.
- John Lee Roche from season 4's "Paper Hearts" is an utterly evil child molester and Serial Killer who killed 16 little girls. He manipulated their parents to trust him, and then came back and kidnapped the girls at night. He plays sick mind games with Agent Mulder and tries to convince him that he took his little sister Samantha (whose disappearance was not explained), even though it's not true. He manages to escape from prison during the re-opened investigation and tries to take another girl. When Mulder catches them, he nearly shoots her. He doesn't regret his deeds at all and would continue if he could.