On September 22, 2004, a plane breaks apart in mid-air, scattering survivors on a remote island somewhere in the South Pacific. Fourty-eight of these survivors, after the initial shock passes, attempt to set up a camp, and figure out where they are, but are disturbed by loud roaring noises and crashing trees emanating from the nearby jungle. Three of the survivors; Jack, Kate and Charlie, set out to find the cockpit. An injured pilot, tells them that the plane had lost radio contact six hours after take off, turned back for Fiji and hit turbulence. The plane was a thousand miles off course when it crashed. The Monster rips the pilot from the cockpit, consequently killing him, and the remaining three run for the beach. Jack, a spinal surgeon from Los Angeles, tries to save an injured survivor. However, he discovers a mugshot of a fellow survivor who he has begun a close friendship with. After initial mistrust and the death of the Marshal, both of them agree to start afresh.

After having opened the Hatch at the end of Season 1, it is revealed to be a research station, which has running water and electricity, is well stocked with food, and has a 1970s era computer, which, according to its previous occupant, Desmond, must have the Numbers 4, 8, 15, 16, 23 and 42 typed into it every 108 minutes, or "the world will end." The computer was broken during the first foray into the Swan station, and Desmond flees, expecting impending doom. The survivors debate whether or not to trust Desmond's instructions, but set up shifts to keep watch and enter the numbers, having repaired the computer. They gradually learn through bits of filmstrip that what they had previously referred to as "the Hatch" is actually the "Swan station", one of several different DHARMA Initiative stations present on the Island.

After the events at the Pala Ferry, Season 3 picks up with Jack, Kate and Sawyer being held prisoner by The Others on another Island. The Others as a group are revealed to be less omnipotent as first thought, who wear normal clothes and have many resources on the island, including electricity, running water and a large supply of food and weapons. Jack is held in an aquarium where he meets Juliet, a fellow Other. Sawyer, in a cage, meets Karl in the cage opposite, but he's moved elsewhere and Kate is replaced. The two of them are forced to do hard labour with the rest of the Others. Ben promises Jack safe passage off the island if he complies to do what they need him to do.

After Jack calls the freighter, the wait begins for rescue. Naomi is clinging to life but eventually dies in front of Kate, who tells her that Locke is the man who threw a knife into her back. Just before she dies, she alerts the freighter in code that she was experiencing trouble. The survivors split into two factions, Jack's group head to the beach to get rescued, whilst Locke and his followers head inland to the Barracks to hide from the freighters, heading Charlie's warning (and Ben's accusation that they're here to kill everyone on the island). Soon, a helicopter is seen flying overhead and a man parachutes from it, introducing himself as Daniel Faraday to Jack and Kate. Daniel is nervous, edgy and unclear, however he mentions that rescuing the survivors isn't their primary objective. The team also includes Miles, a ghost whisperer, Charlotte, an anthropologist, and Frank, who was supposed to be the pilot of Oceanic Flight 815 on the day that it crashed but was replaced for unknown reasons. After continued pressure, Miles admits that the real reason they're on the island is because they want to find Ben. It's later revealed that they were hired by Charles Widmore to find the island. Throughout the season, the survivors don't seem to know whether they're there to rescue or kill them, but it seems the science team were innocent.