'''Season 1, Episode 1''':
-->"It's not an exact science."
-->"It's not ''even'' science!"
--->''[[MadScientist Walter]] and [[OnlySaneMan Peter]] Bishop sum up the entire series''

During a commercial flight from Hamburg to Boston, a virus gets loose and kills everyone aboard, literally rotting the flesh from their bodies while they're still alive. After the autopilot system has put the plane down at Boston Airport, agents from the [=FBI=], the [=CDC=] and the Department of Homeland Security are called in to investigate under the command of [=DHS=] agent Phillip Broyles, the head of what will later be revealed as Fringe Division. Among those investigating are [=FBI=] Special Agent Olivia Dunham, her partner (and lover) John Scott, and her longtime friend Charlie Francis. Olivia is keen to find the cause of the outbreak, but she's given the most menial tasks in the division by Broyles, who has a grudge against her for once investigating and convicting a friend of his for sexual assault. However, while following a seemingly-innocuous lead, Olivia and John discover chemical labs in a lot of storage garages, as well as a suspect. They chase the suspect, who leads them into a trap and destroys the labs with a self-destruct device. Though Olivia isn't close enough to suffer any serious harm, John is caught in the middle of the explosion: not only does he barely survive, but he is also contaminated by some of the chemicals and begins to suffer the symptoms of the virus (the most prominent of which is his skin becoming translucent). The suspect escapes and Olivia, who wasn't close enough to see him properly, can't give a description.

Desperate to save John, whose condition is slowly deteriorating, Olivia researches the symptoms of the virus and learns that a scientist named Dr. Walter Bishop did a lot of research on its effects. For a time, Walter was the leading authority on a branch of theoretical science called "fringe science", studying and researching scientific phenomena that would be considered paranormal, impossible and just plain ridiculous, until an incident 17 years earlier when one of his assistants died in a laboratory accident and Walter was committed to a mental asylum. Olivia wants to get Walter's expertise, but to get him released without the lengthy process of a court order, she needs the permission of Walter's only relative: his son, Peter Bishop, a nomadic con-artist/businessman with a genius IQ[[note]]despite being a high school dropout, he managed to falsify a degree, get a job as a professor at MIT and even publish some research papers before being caught[[/note]] and a roguish disposition. Using the threat of (non-existent) incriminating evidence, Olivia convinces Peter to give her access to Walter, and later to consent to be his legal guardian when Walter is released from the asylum to help in the investigation. As a result of his time in the asylum, Walter is almost completely insane.

Once he's examined John (in his old lab at Harvard University), Walter is able to diagnose the condition much better than any previous doctors had been able, but can't help without knowing exactly what chemicals were in the destroyed lab. The only way to get that information is to find the suspect, but nobody saw him except for John: however, Walter has a solution. He proposes a risky procedure[[note]]He claims to have used the technique to extract information from a corpse, which is possible if they haven't been dead for more than six hours[[/note]] in which Olivia is connected to John, dosed with psychotropics and placed in a sensory deprivation tank, which should allow her to access a shared dreamspace with John and see his memories. The procedure works, and Olivia is able to identify the suspect -- Richard Steig -- as a former employee of Massive Dynamics, a [[MegaCorp multi-billion dollar mega-corporation]] founded by the reclusive scientist William Bell, who was Walter's former partner during the fringe experiments. To find out more about Steig, Olivia meets with Nina Sharp, the Executive Director of Massive Dynamics, who is perfectly willing to help but is coy about the company. Nina briefly mentions something called "the Pattern", but doesn't explain what it means after learning that Olivia doesn't know about it. With information about Steig provided by Massive Dynamics, the [=FBI=] arrest him and learn what they need to know to cure John.

While Walter and Peter work on the cure, Olivia asks Broyles about "the Pattern" that Nina Sharp mentioned. Broyles reveals that the incident on the flight was the latest in a series of [[MadScience inexplicable paranormal events, scientific in nature]], that have been occurring across the planet in recent months. It's known as "the Pattern", and Broyles theorises that it's a series of experiments in which innocent people are being used as guinea pigs. He asks Olivia to join Fringe Division, which has been tasked with investigating the Pattern and its cause, but she refuses. Meanwhile, Walter's cure works and John makes a full, speedy recovery. Olivia questions Richard Steig about the virus and his motives for releasing it: Steig claims it was a demonstration to scare someone who'd been threatening him, someone working for a mole in the [=FBI=] who wanted the virus. To prove his claims, Steig tells Olivia where she can find a recorded conversation with the FBI mole, and she realises that the mole was John all along. As she calls Charlie and the other agents at the hospital, John murders Speig and tries to escape in an [=SUV=]. Olivia gives chase, and during the pursuit John flips his vehicle and suffers fatal injuries. He dies in Olivia's arms. Distraught, shocked, angry and determined to find out what's really going on, she returns to Walter's lab and begs Peter not to leave, but to stay and help her and Walter investigate the Pattern. Even though it goes against his instincts, Peter agrees.

In a Massive Dynamics laboratory, John Scott's body is being brought in. After learning that he's only been dead for five hours, Nina Sharp orders the lab tech to "question him".

!!Tropes present in this episode include:
* AuthorAppeal: Opening a TV series with a plane disaster? Nice to see you again, Mr. Abrams.
* BeardOfSorrow: Walter. Though considering he was in an asylum and somewhat mentally disturbed, it wouldn't be a good idea to give him a razor.
* BodyHorror: The flesh-melting toxin, and its effect shown at the beginning and through the episode.
* TheCallKnowsWhereYouLive: Olivia doesn't want to be part of the Fringe division, especially after she saved John. Sadly, John isn't who she thinks he is, and his death leaves her with a myriad of questions she needs to answer.
* CrypticBackgroundReference: Whatever happened to the prior Fringe team.
* DeaderThanDead: Why corpses more than six hours old can't be questioned through PsychicLink.
* DrugsAreGood: The series sets the tone right out of the gate: LSD is integral to solving the case and saving the day and Walter cooks up his own prescription psychotropics to replace what he was on in the mental institution.
* EpunymousTitle: Pilot [[CaptainObvious because it's the pilot]], and [[StealthPun involves an airplane]]. Coincidence? [[RunningGag Future titles would suggest otherwise.]]
* {{Foreshadowing}}: One quote given by Walter when he re-enters his old lab: "So much has happened here. And so much is yet to". Not only it references to the Fringe Division's work, but also to the fact he knows or knew more than he let on.
** Walter's first line, "I knew someone would come, eventually," also has a disturbing amount of foreshadowing. He knew someone would need to talk to him because eventually [[spoiler:the universe would start breaking down.]]
* JackBauerInterrogationTechnique: Peter induces Steig to talk by smashing his hand with his coffee cup.
* PsychicLink: Of the WeirdScience variety.
* TheSociopath: Richard Steig. The series start with him killing his own twin brother and everyone aboard the plane for ''an experiment''. And aside from Peter hammering his hand with a cup, he is in DissonantSerenity always.
* VorpalPillow: How John kills Steig, who is handcuffed to the bed and was sleeping before getting surprised.
* WeirdScience: Focuses much more on the concept than the [[Series/TheXFiles other dark sci-fi show Fox used to run on prime time.]]
* WhamLine: "We would be happy to treat you as family as well!". John first says it while on the phone when he and Olivia go to the plane incident, but later we learn he was threatening Steig.