Agents of S.H.I.E.L.D. (2013– )
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Season 1 starts several months after The Avengers (2012), as Coulson's "death" in that film, and the destruction in New York, are both referenced.The first seven episodes are also set after the events of Iron Man Three (2013), since the pilot makes reference to Extremis, the drug introduced in that film. Episodes 8 through 16 take place after the events of Thor: The Dark World (2013) (but before Captain America: The Winter Soldier (2014)) since these impact two of SHIELD's cases. The events of The Winter Soldier involve a major twist that leads into episodes 17 through 22.
Season 2 starts some time after Guardians of the Galaxy (2014) and Guardians of the Galaxy Vol. 2 (2017). The first 19 episodes take place some time before Avengers: Age of Ultron (2015), the last three afterwards.
Season 3 starts some time after Ant-Man (2015) (first 19 episodes). The remaining three episodes take place after Captain America: Civil War (2016).
Season 4 starts before Doctor Strange (2016) (first 6 episodes). The remaining 16 episodes take place before Spider-Man: Homecoming (2017).
Agents of SHIELD is part of the Marvel Cinematic Universe, produced by Marvel Studios, a film studio spun off from Marvel Comics and owned by Walt Disney Company.
In the 1990s, Marvel Comics was in need of money and they sold off the film rights to several of what were then their most popular properties. Spiderman was sold to Sony while The Fantastic Four and the X-men were sold to 20th Century Fox. While Sony eventually sold the rights to Spiderman back to Marvel, thus allowing the character to appear in "Captain America: Civil War", the rights for the X-men, and related characters and concepts, including the idea of mutants, are still owned by Fox who still produces movies based on them (most recently, 2016's "Xmen: Apocalypse" and 2017's "Logan").
Instead of mutants, Agents of SHIELD uses the idea of Inhumans, a variation of the mutant concept that was also created by Stan Lee and Jack Kirby originally in The Fantastic Four series, who carry alien DNA which allows them to develop powers when exposed to the Terrigen Mist. Edit
Season One: Hydra (Led by John Garrett aka Clairvoyant and Grant Ward)
Season Two: Hydra (Led by Daniel Whitehall and Grant Ward), Calvin Zabo (Partially), and the Inhumans (led by Jiaying)
Season Three: Hydra (Led by Gideon Malick and Grant Ward), Hive, and the Watchdogs
Season Four: The Ghosts, the Watchdogs (Led by Senator Ellen Nadeer and Anton Ivanov), Eli Morrow, Holden Radcliffe, and the LMDs and Framework Hydra (Led by AIDA/Madame Hydra/Ophelia)
Season Five: The Cree (Led by Kasius), Hydra (Led By General Hale)(Partially), Ruby Hale, and General Talbot
Season Six: Sarge and his crew (Partially), the Chronicoms (Led by Atarah), and Izel Edit
Skye was just an alias she used as a hacktivist under the banner of Rising Tide. Because Skye was dropped off as an infant with no paperwork, she had no idea what her real name was. She found out who she was when she met her father, Calvin, who called her by her real name. In season 3, she chose to be called Daisy Johnson since it was her birth name and it rubbed off on her. Edit
In "The Avengers," agent Phil Coulson is shown being killed by Loki. In the series premiere for Agents of S.H.I.E.L.D., it is explained that Coulson was actually only "dead" for a few seconds and was quickly revived. However, S.H.I.E.L.D. director Nick Fury, well known for his secretive and manipulative nature, told the Avengers that Coulson was dead in order to help rally them to fight Loki.
However, it quickly becomes clear that there is more to the story than this and the big overarching plotline of the first season involves Coulson's attempts to discover what really happened to him. We eventually learn that Coulson was actually dead for an extended period of time after being killed by Loki. Fury ordered him brought back to life via an experimental process which S.H.I.E.L.D. had been developing in case one of the Avengers was killed. This process was extremely traumatic and involved infusions of a serum synthesized from an alien being. To keep Coulson from remembering this, S.H.I.E.L.D. created a cover story and implanted him with false memories of having recuperated in Tahiti. Edit