The prophetic words of the alien Bounty Hunter resonate throughout the fourth season, beginning with the near death of Mulder's mother and the murder of the mysterious X. Even the return of Alex Krycek and the alien black oil are overshadowed by Scully's cancer. Then the tragic reappearance of Max Fenig leads to the death of a fellow FBI agent. Yet even as these events strengthen Mulder's belief in a growing conspiracy, a startling truth revealed to Scully plunges him into a crisis of faith which could prove his ultimate undoing.
Jeremiah Smith and Mulder are on the run from the alien bounty hunter, and Smith takes Mulder to a small farm tended to by identical sets of children, and all the girls are clones of his sister when she was still a child. Mulder prepares to take Jeremiah and one of the clones to see his mother in the hospital, but the bounty hunter catches up with them. Meanwhile, the Syndicate suspects that they have a traitor in their midst and plan a trap which results in X being executed by the Cigarette-Smoking Man.
A baby is found buried alive in shallow ground and appears to have birth defects resulting from generations of inbreeding, leading Mulder and Scully to a reclusive family who have a history of inbred children.
After several African-American men are killed and the color is drained from their skin, Mulder learns about the Teliko, an African folktale about a creature who must suck the pigmentation from a persons body in order to survive.
Several kidnappings of young women linked by distorted photographs lead Mulder and Scully to a man who can imprint his darkest fantasies onto undeveloped film and is trying to save the women from the "Howlers".
After an FBI raid on a doomsday cult called the "Temple of the Seven Stars", Mulder meets Melissa, a cultist who claims to have known him in a previous life during the American Civil War. Scully believes the woman is a delusional schizophrenic, but Mulder allows himself to be drawn into her fantasies.
A link to the four witches Sabbaths is found after a doctor loses control and kills a patient on the operating table, and Mulder suspects a nurse may be practicing witchcraft.
Frohike pieces together and recites to Mulder and Scully what could be the possible life story of the Cigarette Smoking Man; from a young captain in the U.S. Army recruited to assassinate President Kennedy, to becoming the mysterious man in the shadows at the height of a global conspiracy. What measures will the Cigarette Smoking Man take to ensure that he remains a mystery forever?
A rock sample taken from Mars is intercepted at an airport and infects a security officer with the Black Cancer, while Mulder is given a tip about potentially dangerous paramilitary operations but is doubtful when the informant turns out to be Alex Krycek. Reluctantly, Mulder accepts Krycek's help and tracks the rock to Russia where he discovers an elaborate test being performed by Russian scientists.
While imprisoned in Russia and infected with the Black Cancer, Mulder learns that Krycek is working with the men responsible and everything has been a setup from the start, while Scully and Skinner are called to a suspicious Senate hearing where the only question is the whereabouts of Agent Mulder.
Mulder's dreams help him in finding the body of a little girl which reopens one of his old cases in the Violent Crimes Unit and leads him to believe the killer he captured had more victims and may have taken his sister many years before.
A strange yellow rain kills a migrant girl, and her family believes that a mythical creature was the cause and has manifested itself inside the brother of her fiancé, who has since disappeared.
After the body of a decapitated EMT disappears from the morgue and an identical man starts work at the same hospital, Mulder believes that the man has the ability to regrow parts of his body, including his head. The agents soon discover that Betts' body is riddled with cancer and he is able to live in that condition but needs to feed on cancerous tumors to keep up his strength.
While Mulder is forced to take a vacation he leaves Scully with an assignment to keep her busy until he returns. However, she decides to start living and goes on a date with a man who believes that his tattoo talks to him and is telling him to stay away from other women.
Scully's recent failing health is revealed to be inoperable brain cancer, which is common among abductees. She meets with other abductees with the same condition and forms a special bond with a dying woman, while Mulder tries to save her from a doctor who may be connected with the abductions.
Issac Luria, a Jewish man, is killed by a group of teenagers working for a racist shop owner, but one of them is soon strangled to death, and the fingerprints on his neck are from Issac. Despite other factors, Mulder becomes convinced that the man has returned from the dead to exact revenge.
When a U.S. military general is inexplicably murdered in the back of his limousine, a paramilitary group is suspected. They believe it was a soldier who they liberated from a Vietnam POW camp and is plotting to kill certain corrupt military figures.
While celebrating Scully's 33rd birthday, a strange woman informs Mulder that NICAP member Max Fenig (see Fallen Angel) has recently died in a plane crash. After a visit to the crash site and finding Max's body with radiation burns on it, Mulder suggests that the plane was intercepted by a UFO and is rapidly being covered up by the military.
Mulder is arrested for investigating the plane crash and interfering with a military operation, while Scully is caught in an attempted assassination of Corporal Frish which claims the life of Agent Pendrell. Scully bails Mulder out of prison, and they go to Max Fenig's trailer to find out why he was on the plane. Mulder finds evidence of alien technology and boards a plane with it, but the plane is intercepted mid-flight and it disappears. Mulder is again left with nothing.
A case involving a strange old man warning two scientists of events in the immediate future which come to pass (and the use of their experimental flash-freezing compound that does not exist yet) has Mulder believing that one of the scientists has come from the future to stop his own scientific breakthrough from becoming reality.
Five babies in the same town are all born with tails and the local OB-GYN is blamed for tampering with fertilized eggs. However, Mulder discovers the culprit to be a simple man with a genetic deformity who may have the ability to alter his appearance.
Skinner destroys evidence to cover up a woman's death and poses as Agent Mulder to complete the task. Mulder finds out about Skinner's deception and confronts him, and Skinner reveals that he is working for the Cigarette-Smoking Man in order to obtain a possible cure for Scully's cancer.
After a man sees a woman trapped inside a bowling alley pin setter, he goes for help and finds police standing next to a body of the same woman. Mulder and Scully join the investigation and follow up this lead which the police won't bother with, and they are led to a mentally challenged man who works at the bowling alley.
Mulder undergoes an experimental form of hypnotherapy to recover his memories about his sister's abduction, but the treatment has side effects including psychotic behavior, and Mulder wakes up one morning in a motel room with someone else's blood all over him.
While investigating the discovery of a preserved alien body found in the mountains of Canada, Mulder is contacted by Michael Kritschgau. He tells Mulder about a government conspiracy to make people believe in aliens without question, and Mulder has been the prime target.