When death row inmate Luther Lee Boggs claims to be psychic and can lead Mulder to a serial killer in return for a lesser sentence of life in prison, Scully becomes an unwilling believer when Boggs tells her that she can communicate through him with her recently deceased father.

When Mulder finds out that Scully was kidnapped by Duane Barry, he risks the wrath of his superiors and the annoyance of Agent Krycek in order to do whatever it takes to find her. Meanwhile, Krycek is found to be reporting Mulder's activities to the Cigarette-Smoking Man.

Scully mysteriously appears in a Washington hospital, alive but in a coma, and Mulder must fight to keep her alive in order to find out what happened to her and who did it to her. Meanwhile, Scully fights her own personal battle as she decides whether to stay or go on to the next world.

Scully finds her career with the FBI in jeopardy as Mulder is still missing and the Cigarette Smoking Man is pursuing the stolen files. The Navajo elders find Mulder's body in a cave and perform an ancient ceremony to call the spirit back to the empty vessel.

A.D. Skinner and Scully are at a standoff when Mulder bursts in and discovers that Skinner has the digital tape. Reunited, Mulder and Scully travel to a secret vault inside a mine and find an elaborate filing system of medical records which reveals that Mulder's sister may not have been the first choice for abduction. Meanwhile, Skinner deals with the Cigarette-Smoking Man for their safety.

Mulder and Scully investigate a series of murders linked to a mysterious device that alters television signals causing paranoid hallucinations. One of them falls victim to it.

Scully's recent failing health is revealed to be an inoperable cancer in her skull, which appears to be common among abductees and she attempts to come to terms with her condition. Meanwhile, Mulder and the Lone Gunmen break into a high-security research lab to find the cure that could save her life.

Mulder fights to prove that a discovery frozen in the mountains of Canada is an irrefutable evidence of alien life, but his quest for the truth only leads to more lies and an unthinkable conclusion.

The Cigarette-Smoking Man helps Mulder to obtain Scully's cure and also lets him see his real sister who doesn't turn out to be as happy to see Mulder as he would've liked. In return for this, the Cigarette-Smoking Man asks that Mulder quit the FBI and work for him in the Syndicate where he could have power and respect which Mulder turns down, deciding to stay on the side of justice. While Scully's cure appears to have worked, the Cigarette-Smoking Man faces his own enemies and disappears, presumed dead.

On her Christmas vacation with her brother's family, Scully receives a mysterious phone call from a familiar voice who says, "She needs your help. Go to her." The phone call leads Scully to a murder case where the victim's 3-year-old adopted daughter bears an uncanny likeness to her sister, Melissa, at that age. The emotional roller coaster that follows has Scully believing that her sister had a baby during a period when she traveled the country and she tries to adopt the child, knowing that caring for the little girl would change her life.

DNA testing on Emily reveals that she is actually Scully's daughter and Mulder comes to assist her and to find out where and how the girl was born while Scully tries to help Emily with her own serious illness, a rare form of anemia.

Shortly after Mulder is buried, Billy Miles is found very dead, but he somehow comes back to life. Skinner and Scully put all their hopes into digging up Mulder and discovering that he too, is still alive. As Mulder lies in the hospital without indication that he is going to fully recover, Krycek comes to Skinner and offers him a vaccine to the virus that has infected Mulder, but the cost of the vaccine is that Skinner has to kill Scully's unborn child.

Mulder and Doggett join forces to investigate the arson attack on a genetics lab where one of the doctors suspected of experimenting with alien impregnation is killed. They encounter Billy Miles, who has been changed into an alien replicant after his recent abduction and is attempting to erase evidence of the tests. When a woman helping Scully out at home is found to be a part of the conspiracy, the agents, along with Monica Reyes and Alex Krycek, know they must protect Scully and her baby from Billy Miles and get her out of the city.

Agent Doggett investigates the death of an EPA official after his car is forced off a bridge by a woman he picked up. He asks for assistance on the case from Scully, who has returned to her teaching position at the FBI Academy in Quantico.

When pieces of the spaceship beached in Africa resurface, the conspiracy within the FBI attempts to hide the information from the X-Files, especially the one person for whom the pieces have a special significance - Scully. When Doggett and Reyes discover that Scully and her child have been put in great danger, they race to protect her and William from the evil forces pursuing him, and Scully is forced to take drastic measures to protect her child.

Mulder and Scully investigate the murder of a city official, a crime that doesn't appear to have been committed by human hands. Meanwhile, Scully faces deeply emotional feelings about the child she gave up for adoption.