Sydney's life is in mortal danger as she is sent to Madrid to retrieve a 500-year-old sketch that contains a set of numbers and meets up with her deadly nemesis, K-Directorate agent Anna Espinosa. Meanwhile, Will delves deeper into the cause of Danny's death and discovers a very strange anomaly.

While helping Shepard escape from the asylum in Bucharest, Sydney discovers the shocking connection he has with her past. Meanwhile, after tracking the computer virus secretly planted by the CIA, Sloane is confronted by Alliance representative Alain Christophe, who suggests that one or more moles may have infiltrated SD-6. Will continues to investigate the woman claiming to be Danny's mistress and Sydney finds out the truth about her father's involvement in her mother's death 20 years earlier.

Sydney and Dixon are sent to Las Vegas to gather information from a K-Directorate agent who has ties to the group that attacked and nearly destroyed SD-6. Meanwhile, Sydney learns some shocking news about Francie's fiancé, Charlie, Will begins his journey in discovering what SD-6 really is, and Jack continues to try to be more of a father to Sydney when he helps her decide whether or not to continue with graduate school.

While on a case to track the activities of Khasinau, a.k.a. "The Man," Sydney runs into her ex-lover, Noah Hicks, who broke her heart and left without saying goodbye five years earlier. Meanwhile, Sydney tells Sloane that she wants to find her mother; Jack is ordered to see CIA psychiatrist Dr. Barnett to help him deal with his churning emotions after discovering that his wife may still be alive; and Will and Francie become suspicious of Sydney's activities after finding one of her airline ticket stubs.

Sydney must outwit Sark in order to find a crucial piece of intel. Meanwhile, Jack faces Sydney's mother for the first time in almost 20 years. Will finally meets Vaughn and Sloane is haunted by his wife's death.

Sydney's trust in her father begins to fade. Meanwhile, Sydney and Vaughn may have been exposed to a deadly virus while in Taipei; Sloane haunted by Emily's death begins to unravel. Vaughn enlists Will to help research a case.

Jack meets Alliance counterintelligence head Ariana Kane, who is sent in to investigate Emily's disappearance and to discover who is trying to blackmail Sloane. Meanwhile, Marshall is sent on his first mission with Sydney as his partner. Vaughn schedules Will to take a CIA psych test. Francie gets suspicious over Sydney and Will's secretive behavior.

Sydney, Vaughn and Jack must determine whether CIA agent Lennox is who he says he is after his deep cover mission is compromised.

Sydney must make a life-defining decision regarding her future with the agency, while Sloane re-emerges and continues his obsessive quest to piece together the mysterious Rambaldi artifacts - with the reluctant aid of a kidnapped scientist. Meanwhile, Dixon's marriage is put to the test after he tells his wife the truth about his occupation.

Sydney's search for her past leads to a jailed Sark, but their Q&A is cut short when he becomes the ransom for a pair of abducted CIA scientists, whose kidnappers may be tied to the murder of his father. Jack contacts an old friend of sorts for info on Sloane's new world-peace project, and Vaughn makes a decision about his future as an operative.