Having woken up in Hong Kong, with no memory for the last two years (!), Sydney returns to Los Angeles to try to piece together the last two years of her life and discovers the fates of her friends and family: Vaughn has married thinking that Sydney was long dead; Marshall is having a baby with CIA tech expert Carrie Bowman; and Dixon is now the new division head of the L.A. office branch of the CIA. Sydney also learns the shocking fates of Jack and Sloane; the former is in CIA custody for communicating with Irina whom still is in hiding, while the latter is living in Switzerland under house arrest in exchange for co-operation with the CIA. Sydney is granted temporary CIA clearance on a case that may help her regain her memory and she meets a new enemy group called The Covenant.

Sydney and Vaughn are reunited again as a team to prevent Sark, now a head leader of the Covenant, from destroying the nation's satellite communications system. Meanwhile, Jack must find a way to stop Marshall from uncovering the identity of a murderer suspect whom is Sydney. Also, Sydney accompanies Vaughn and his wife, Lauren, as they meet with Sloane to ask for a favor.

After making a shocking discovery of a severed human hand in the desert that belonged to Lazarey, the Russian diplomat she murdered while working as a brainwashed assassin for the Covenant, and who may in fact be alive, Sydney agrees to submit to an experimental procedure conducted by an eccentric doctor, named Dr. Brezzel, designed to retrieve her lost memories. But while Jack and Vaughn look on, Sydney's mind proves surprisingly resistant to letting her remember her missing time... and the process of recovering it could end up killing her. Meanwhile, Lauren makes a great sacrifice of allowing herself to get tortured and beaten up in order to make her alibi believable to Lindsey after helping breaking Sydney out of NSC custody. Also Sloane finds himself boxed in by an unlikely enemy, that of Mr. Lindsey, who wants to see Sydney Bristow eliminated permanently.

The identity of the mysterious "St. Aidan" forces Sydney to pull a stunned Will Tippin out of witness protection for help in finding Lazarey to clear her name. But the pursuit sends the two old friends on a collision course with Allison, the Francie impostor who ruined both their lives. Meanwhile, a jealous Lindsey arrests Jack and Vaughn as conspirators in Sydney's escape from NSC custody. Sloane, still under pressure from Lindsey, puts a plan in motion to eliminate Sydney, and Dr. Brezzel has an unpleasant run-in with Sark whom is also looking for Sydney.

In this episode, Sydney finally learns the shocking truth about her missing two years from an unlikely source: FBI Special Officer Kendall. Kendall whisks her away and talks to her from the privacy of an airborne 757 jet. According to Kendall, Sydney was captured by the Covenant after her fight with Francie/Allison, held captive in Russia for over a year and brainwashed to become an assassin. But Sydney only pretended to be brainwashed and contacted Kendall who became her contact and handler, thus giving him information about the Covenant and about their quest for Rambaldi artifacts. Sydney also staged the murder of Andrian Lazarey, and then deliberately had her memory erased to prevent the Covenant from knowing about secrets she had learned about Rambaldi's findings.