Fringe follows the casework of the Fringe Division, a Joint Federal Task Force supported primarily by the Federal Bureau of Investigation, which includes Agent Olivia Dunham; Dr. Walter Bishop, the archetypal mad scientist; and Peter Bishop, Walter's estranged son and jack-of-all-trades. They are supported by Phillip Broyles, the force's director, and Agent Astrid Farnsworth, who assists Walter in laboratory research. The Fringe Division investigates cases relating to fringe science, ranging from transhumanist experiments gone wrong to the prospect of a destructive technological singularity to a possible collision of two parallel universes. The Fringe Division's work often intersects with advanced biotechnology developed by a company called Massive Dynamic, founded by Walter's former partner, Dr. William Bell and run by their common friend, Nina Sharp. The team is also watched silently by a group of bald, pale men who call themselves "Observers".
Season 1 introduces the Fringe Division as they investigate cases that form "the Pattern", many orchestrated by the bioterrorist organization, ZFT (Zerstörung durch Fortschritte der Technologie, or in English, Destruction through advances in technology). Olivia comes to learn she was a child test subject for Walter years ago for a nootropic drug, Cortexiphan, giving her weak psionic abilities. Walter also struggles with adjusting to normal life in Peter's care after living several years in a mental institution, and hides a secret about Peter's past from him.
In Season 2, the occurrences are found to be in conjunction with activities of a parallel universe, which is plagued by singularities occurring at weakened points of their world. The Fringe team deals with more cases that are leading to a "great storm" as the parallel universe appears to be at war with the prime one. Walter is forced to tell Peter that he is from the parallel universe, a replacement for his own Peter that died from a genetic disease, and that it is his prior experiments that caused the singularities in the parallel universe.
Season 3 presents episodes that alternate between the two universes. "Walternate", Walter's doppelgänger in the parallel universe, has set events in motion to assemble a doomsday device that reacts only to Peter's biology, sending his Olivia, "Fauxlivia", into the prime universe in Olivia's place, get close to Peter, and guide them to find the doomsday device's prime universe counterpart. Olivia, trapped in the parallel universe, is subjected to experimentation by Walternate to explore her Cortexiphan-induced abilities. She is able to escape to her own universe using her psionic abilities and expose Fauxlivia to Peter. Fauxlivia is extracted to the parallel universe, having withdrawn a critical component of the doomsday device, and, through accelerated development, gives birth to Peter's child. In the prime universe, Olivia and Peter resolve their relation due to Fauxlivia's involvement, while evidence of weak points in the fabric of reality start to develop.