The action explodes in the phenomenal fourth season when Sydney leaves the CIA to join a powerful new Black Ops unit, having no idea of the reunion in store for her.
Sydney quits the CIA and joins a Black Ops unit called "Authorized Personnel Only" alongside Dixon, Jack, Vaughn and... Sloane. Meanwhile, the truth Sydney found out in Wittenberg endangers her relationship with Jack, and eventually she reveals the awful truth to Vaughn.
Sydney unwillingly teams up with her father to hunt down a modern-day samurai. Meanwhile, Nadia doesn't want to go back to the spy business, but is forced to when Sydney's life is jeopardized. Sydney finds out the reason behind Jack's misdeed and Nadia makes an unsettling promise.
Sydney must seduce a murderous arms dealer in order to track down a stolen NSA code-breaker. Meanwhile, Vaughn fears for Weiss's life, and Sydney and Jack argue about telling Nadia the truth about her mother.
Sydney and Vaughn go undercover to track down a deadly new bio-weapon. Meanwhile, Sydney is concerned about Vaughn not having yet put Lauren behind, and Nadia turns to a Jack to find out the truth about her mother.
Sydney and Vaughn go undercover as a married couple so as to find a weapon that could bring back the Dark Ages. However, the neighborhood they've infiltrated is not as charming as it seems.
After being infected with a hallucinogen, Sydney starts to lose touch with reality. Vaughn and Jack must rush to find an antidote before Sydney puts her life - and others next to her - into danger.
While Sydney and Nadia argue about Nadia's acceptance of Sloane's fatherly concerns, Sloane worries about Nadia's well-being when she and Sydney go undercover as wealthy, irresponsible young heiresses to uncover the whereabouts of a deadly chemical.
Sloane temporarily steps down as Director of his Task Force and gives Jack full authority over the next assignment, which involves Anna Espinosa, Sydney's old foe. However, Anna turns the tables on APO when she captures Nadia and forces Sydney to do her biddings. Sydney tells Nadia about the Rambaldi's prophecy which dictates that two sisters will fight and only one will survive. Meanwhile, Vaughn visits Sark and tries to trick him into helping them to catch Anna. In the end, one of the sisters is mortally wounded by Anna.
While Nadia is in a coma, Sark is taken into APO to help them infiltrate Cadmus Revolutionary Front and retrieve the bomb, but in return he demands to see Lauren's corpse and that Vaughn opens her coffin for him. Nadia may be the only person with the intel they need to intercept the bomb, so Jack is forced to prematurely wake Nadia from her coma, endangering her life, which doesn't please Sloane when he finds out.
Dixon enlists Sydney to help him prove that Sloane is double-crossing the CIA and using APO to steal the Blackwell Index, a master blackmail list, and to reconstruct the Alliance. Sydney makes her way into Sloane's house so as to copy the encryption key from his secure phone and crack his calls. When Nadia finds her, she becomes disappointed in her sister. Meanwhile, Vaughn discovers something disturbing about his father when he visits his comatose uncle.
Sydney must protect the life of a civilian, whom she unintentionally put in danger. Meanwhile, Jack plans a visit with an old friend, and Vaughn uncovers more disturbing secrets about his father.
Nadia puts her own life - as well Sydney's and Weiss's - in danger after failing to unveil her past through a dangerous criminal. Meanwhile, Vaughn finds a person who is somehow connected to his father and Nadia as well.
When a mission goes wrong, Sydney's is placed in danger and Marshall is the only one who can save her. Meanwhile, Dixon is exposed to a deadly pathogen released inside APO.
Sydney and Vaughn risk their lives trying to find out the truth about Vaughn's father. Finally, we find out why Jack and Sloane seem to be conspiring together against Sydney and Vaughn.
In an attempt to talk to Sydney, Katya Derevko deliberately poisons herself and is temporally taken out from her cell. Once Nadia tells her sister about this, Sydney visits her aunt to tell her to stay away from Nadia. However, Katya unsettles Sydney by telling her that someone framed her mother as a means of getting her killed. Sydney sets off in search of the truth behind this story. Meanwhile, Vaughn becomes a rogue agent by getting involved with the people who might know his father's whereabouts. In the end, he and Sydney find out that the man behind these two plots is no other than A. Sloane. However, things are not exactly as they seem to be.
Sydney and Vaughn tell Jack about Sloane's alleged involvement in Vaughn's search for his father and Irina's contract on Sydney's life. After cornering Sloane, they both conclude that someone is framing him. The APO team set a trap to catch the fake A. Sloane, but they fail. Once they realize what "Arvin Clone" is after, Sloane suggests he should step down temporarily. However, Sydney reluctantly convinces him to stay on the case, since he may the only person able to anticipate "Arvin Clone's" next move. But Nadia fears that this pursuit may revive her father's past obsession – Rambaldi.
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 – Elena Derevko, the third and the most cruelest of the Derevko sisters, has been surveilling 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. 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 play her own mother. Meanwhile, Sophia moves in with Sydney and Nadia.
The team captures the Sloane Imposter and questions him to find a rare Rambaldi orchid. The real Sloane must relive a painful memory in order to get the Imposter to reveal the orchid location.
After a tactical group infiltrates the DSR and steals Rambaldi artifacts, CIA director Hayden Chase discovers that the alarms at the DSR were disabled from Nadia's computer, allowing the raid to happen, and 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 Syd and Nadia, is Elena Derevko. They follow her trail to a dead Rambaldi follower, a stunning betrayal, and a presumed dead family member...
Rambaldi's catastrophic endgame begins to fall into place as a giant red ball version of the Circumference/Mueller device is found floating over a large city in Russia, driving the citizens mad with violence. After a wounded Dixon reveals that Irina is alive, Sydney, Nadia, and Jack set off to find her.
Jack, Sydney, Irina, Vaughn and Nadia parachute into Sovogda. They're supposed to dismantle a giant red ball turning people into zombies. At APO, Marshall and Weiss use the Blackwell Index to blackmail the Russian minister into giving them the access codes to a Russian satellite, they discover that Elena is uplinking the satellite. A CIA agent, Brodien reminds them that the Rambaldi device is broadcasting a subaudible frequency that physiologically alters people who drink it and it is irreversible. Elena learns of the APO team's arrival.