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After the Battle of New York, Phil Coulson is alive, to the surprise of anyone who saw him die in The Avengers. He says he spent a few days recovering in Tahiti, a magical place. Coulson puts together a small team aboard a plane called the Bus: pilot Melinda May, field agent Grant Ward, and scientists Fitz and Simmons. Soon Skye joins them, a hacker who lives in a van and belongs to a group that wants to expose S.H.I.E.L.D. She becomes a consultant and, little by little, an agent.
The early cases involve people with powers and dangerous tech, most of them tied to Project Centipede. The group mixes Extremis, the super-soldier serum, and gamma radiation to build soldiers. Mike Peterson, an out-of-work dad, is one of its test subjects. Behind Centipede are Raina, the woman in the flower dress, and a mysterious boss called the Clairvoyant, who seems to know everything. Skye hunts for clues about her parents and learns she came to S.H.I.E.L.D. as a baby, labeled a 0-8-4, origin unknown.
The gaps in Coulson's memory keep getting stranger. He learns he was dead for days and was brought back by Project T.A.H.I.T.I., using a drug taken from a blue alien corpse. His Tahiti memories were fake. When Skye is shot twice, Coulson uses the same drug to save her, and the questions only grow.
Then comes the twist. The events of Captain America: The Winter Soldier reveal that Hydra had been hiding inside S.H.I.E.L.D., and the agency falls apart. On the team, the blow is personal: Ward is Hydra. He kills agents, Victoria Hand among them, and shows his loyalty to John Garrett, a veteran agent who was the Clairvoyant all along. Garrett is dying and wants the alien drug to save himself. With no agency, no money, and the government hunting them, Coulson's team goes into hiding.
In the end, Ward drops Fitz and Simmons to the bottom of the ocean inside a pod, and Fitz comes out of the rescue in bad shape. Coulson, May, and Skye take on Garrett with help from Mike, now Deathlok, and Coulson destroys Garrett. Nick Fury shows up and names Coulson director of a new S.H.I.E.L.D., to rebuild from scratch. Two threads are left open: Skye's father, a violent man, is looking for her, and Coulson starts carving strange symbols into a wall, just like Garrett did.