Three years after the attack on the President, Jack Bauer is once again called into duty for his country when terrorists threaten a biological attack if a prisoner is not freed. The terrorists dump an infected body off with Dr. Sunny Macir at Los Angeles Health Services to prove their ability to do so.
A teenager being used as a mule inadvertantly hinders Jack and Chase in their effort to trackdown the virus. Dr. Macer displays the virus's potency for the President.
Jack gets to Kyle Singer's house, but not before Kyle leaves with the virus. Wayne tries to help prepare Palmer for an upcoming debate and some potention hot-button issues. CTU brings in a new person to help prepare against the viral threat.
Palmer outright refuses Jack's suggestion that the President open negotiations with terrorists because he sees it as a step that would make America open to further attacks. Tony is caught in a life-death situation after suffering a gunshot as Michelle worries over his fate. Jack takes down Chase to free Salazar and, in the process, starts a prison riot.
Jack tries to secret Ramon out of the prison under cover of the riot. CTU closes in on the missing Kyle Singer. Palmer and Senator Keeler square off in a debate.
Ryan Chappelle assumes control of CTU in Jack's absence even as President Palmer must decide whether to shoot down the helicopter Jack and Salazar are using for their escape. Jack's drug use is outed to Kim and the CTU. Upon delivering Salazar, Jack is taken hostage. Kim learns the identity of the double agent at CTU.
Ryan Chappelle makes an accusation to Chase about whether or not she's covered up Jack's drug addiction. Gael oversees the activity of the counter-terrorist unit when Michelle gives him the full authority to take charge.
President Palmer lets Jack and Tony have it for not informing him of their plan. Hector and Ramon take on each other over Jack's future.
Jack's past continues to haunt him when an unlikely bidder emerges on the billion dollar virus. Wayne's job is in trouble when a large Palmer supporter discovers that Wayne had relations with his wife.
Palmer has to fend off a former supporter who has turned against the President because of Wayne's intimacies with the supporter's wife. The Salazars try to break Chase to get information on CTU's virus plans.
Jack works with the Salazars and Nina to get ahold of the virus. CTU extracts Chase out from under the Salazars, but not without cost. Palmer learns the price of Sherry's assistance.
Nina tries to play Ramon against Jack by bringing his true loyalty into question. Sherry hatches a plan to take down Miliken but it will require Palmer's assistance.
Chase expresses his anger about Jack leaving him out on his plans leading Jack to lecture Chase on the role of the CTU Agent. Nina attacks CTU as only she can.
Chappelle worries that the drugs might interfere with Jack's ability to handle his job. The past comes back to haunt Chase even as Sherry tries to escape her ties to Alan Milliken.
Jack is questioned of his murderous actions against a key witness. Sherry comes under police investigation for her involvement with Alan Milliken.
Jack lets Amador slip through his fingers in order to learn who he's working with. CTU quarantines a hotel where the virus has been released causing the guests to panic and riot. Sherry plays Palmer, having him create an alibi for her.
Jack discovers ties to Stephen Saunders even as the man, once presumed dead, tries to pull President Palmer's strings.
The terrorist involved in the virus outbreak demands the death of Ryan Chappelle and Palmer turns to Jack to deliver the body. Michelle tries to offer a better solution to the infected guests of the hotel in the form of suicide capsules.
Jack tries to gain leverage over Saunders as the rest of the CTU team hunts down the infected man who escaped the hotel before lockdown.
Jack tries to get Saunders's daughter to reveal information about him. Saunders says he will release the virus in a second place if Palmer doesn't follow orders and yield the identities of overseas agents. CTU tries to find the missing infected hotel guest even as the virus starts to seep out into Los Angeles in his wake.
Tony is put in a precarious position as Saunders holds his wife hostage and tries to barter for the return of his daughter. Sherry visits Senator Keeler with information he can use against Palmer.
Jack continues to attempt to prevent Saunders from another release of the virus by controlling his daughter, but when Tony goes rogue to save his wife, this plan comes under strain. Jack reels Tony back in and tries to orchestrate the exchange of Saunder's daughter for his wife. Senator Keeler challenges Palmer with the information he was provided by Sherry and asks for his resignation.
Jack learns that Saunders still plans on having the remaining vials with the virus released. Sherry tries to pull the strings on Palmer.
Tony's actions regarding Saunders and Michelle leave him facing treason charges. Gael's widow takes justice into her own hands, leaving CTU without Saunders to identify the man carrying the virus to its Los Angeles destination.