Sydney teams up with Renée - a fugitive on the CIA's most wanted list -- to track down the murderer of a close friend before the killer can strike again. Meanwhile, Jack enlists a reluctant new agent, Thomas Grace (Balthazar Getty), and Weiss struggles to decide whether or not to accept a promotion that would force him to leave his colleagues.

Sydney and Tom discover that Renie has stolen the cryo container, and soon find themselves under siege by a group of mercanaries who want the contents of the container. Meanwhile, Sloane takes matters into his own hands to get himself back into APO.

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.

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.

Marshall reports to Jack that a microchip, found in Renée Rienne's body, is etched with the name 'Andre Micheaux'. Peyton tells Sloane that Sydney is being sent to Nepal to meet with someone regarding the chip. Sloane sends Anna, now Sydney's doppelgänger, to intercept. When Marshall discovers that the APO office is bugged, Jack frantically tries to reach Sydney to warn her before it is too late.

Sydney and APO attempt to discover whom Gordon Dean is working for and what their end game is. Meanwhile, when the group claiming to have a cure for daughter Nadia continues to play mind games with him, Sloane struggles for control.

Sydney now posing as Anna, brings Peyton a microchip with a device hidden in it. Meanwhile Sloane finishes translating page 47 and reports that only the chosen one can complete the circle, which leads Sark and Sydney on a dangerous mission to a prison. Rachel finally discovers Tom's secret about what happened to his wife.

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 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.

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.

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'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.

After learning that the man she has known as Michael Vaughn is under investigation and suspected of being a double agent, Sydney begins to question whether their business and personal relationship over the years had all been a lie.

While Sloane awaits the outcome of his sentencing, Sydney's life is put in grave danger when Gordon Dean discovers that Rachel is still alive.

Rachel receives a little help from Syd for her first solo mission while Sloan is back at APO in frequent contact with Gordon Dean.

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.

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.

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 is forced to partner on a mission with new APO agent Thomas Grace. They discover that Rachel Gibson -- a spy suspected of being involved in activities against the U.S. -- has something shockingly in common with Sydney.

Rachel and Sydney have to join forces with Julian Sark to prevent a deadly micropulse bomb from falling in the hands of a dangerous mercenary.

While the gang starts to learn more about the Prophet 5, Sloane is distressed to learn that Prophet Five's cure for Nadia is just as likely to kill her. Meanwhile, Devlin returns, the search for Anna Espinosa continues, Rambaldi's prophetic Page 47 resurfaces, and Sydney offers Renée a job at APO.

Sydney's dealings with her mother lead Jack to take drastic measures to ensure his daughter's safety. Meanwhile Will is confronted by a mysterious woman about resurrecting his story on SD-6.

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.