Nadia puts her own life (as well Sydney's and Weiss's) in danger after failing to unveil her past about her involvement with a dangerous criminal, named Ceasar Martinez from her home in Argentina whom recruited her as an assassin for his gang and wants to relive old times. Meanwhile, Vaughn finds a person who is somehow connected to his father and Nadia as well.

Nadia's former caretaker, Sophia, has been severely beaten. She contacts Nadia and asks to meet her. Sloane is told by Sophia that she was beaten up, because someone is trying to track Nadia down, so he and Jack decide to tell their daughters the truth. It turns out that Elena Derevko, the third and the cruelest of the Derevko sisters, has been surveying both Sydney and Nadia for a decade. Meanwhile, Jack's doctor advises him to tell Sydney about his illness.

Jack's illness has caused him to hallucinate about a cure among other things. As a result, Sydney must recreate the time when Jack was working for the CIA and hid the only man who might be able to help him now. For this, Sydney must role play her own mother. Meanwhile, Sophia moves in with Sydney and Nadia.

After a tactical group infiltrates the DSR and steals all the Rambaldi artifacts, CIA director Hayden Chase discovers that the alarms at the DSR were disabled from Nadia's computer, allowing the raid to happen. Mrs. Chase shows up at the apartment to question her. Soon Sloane and Jack arrive and suspect that Sophia, who had access to the computer while she was living with Sydney and Nadia, is in fact Elena Derevko. They follow her trail to a dead Rambaldi follower, a stunning betrayal, and a presumed dead family member when in a surprising twist, Sydney and Nadia learn that Irina Derevko is in fact alive.

Jack, Sydney, Irina, Vaughn and Nadia parachute into Sovogda, Russa to dismantle the giant floating red ball of the Circumfrence which is turning people into mindless, red-eyed zombies out to kill. Back at APO, Marshall and Weiss try use the Blackwell Index to blackmail the Russian defense minister into giving them the access codes to a Russian satellite before the local authorities plan to drop a nuclear bomb on the city to destroy it and prevent the spread of the contagion, and they also discover that Elena is up linking the satellite. In the ruins of the city, a CIA agent, Brodien (the one whom Sydney rescued from Shanghai in the season opener) reminds them that the Rambaldi device is broadcasting a sub audible frequency that physiologically alters people who drink the water-like fluid that has infected the city's water supply and it is irreversible. At the same time, Elena learns of the APO team's arrival and sends Sloane and her men to go out to kill them, leading to a three-way war between Elena's henchman, the APO group, and the zombies leading to Nadia becoming infecting and having a final one-on-one confrontation with Sydney atop a building with the red ball Circumference in the balance.