Tony interrogates Nina about Alvers' location, while Chappelle orders Jack to undergo a medical examination in light of his drug use. Kim and Chase have a conversation about the baby. Palmer confronts Sherry about Alan Milliken's death, while Julia begs Wayne for help.

Palmer and Chappelle view a message from Jack, explaining his undercover work with the Salazars. Meanwhile, Hector tries to convince Ramon that they should deal with Bauer so that they can get their hands on the virus. Jack has a private moment with Claudia and she blasts him for leaving her behind when he arrested Ramon. Chase arrives in Mexico, but is captured by Hector's men. Ramon devises a way for Jack to prove his loyalty to them. Anne manages to clear Palmer's name, but she breaks off her relationship with him.

Palmer clears Anne's name with the press, but he finds that he is facing a new problem when his biggest campaign contributor reveals a startling secret about Wayne. Kim and Michelle worry about Tony's mental ability when he continues to make mistakes. Jack and the Salazars meet with Amador, but the deal turns sour when Nina Myers appears on the scene and competes for the virus.

As the day stretches into the middle of the night, Jack and the FBI formulate a plan to prevent further terror attacks. Events take an unexpected turn when the politics surrounding the administration expand beyond the White House.

As Jack's day enters the early morning hours, the nation remains vulnerable, and President Taylor presses on with her international peace process. With the possibility of colossal failure facing CTU, attention turns to who is to blame, and things get personal when operatives take matters into their own hands.

Jack and Chase quarrel over Chase's relationship with Kim. Meanwhile, they learn of a lead to the possible whereabouts of the virus after raiding a crack-house. Linda breaks up with Kyle when she learns that he is planning to make a drug delivery. Wayne approaches Palmer with information about his girlfriend that could damage his chances for re-election, while a CTU employee is not what he seems.

Claudia manages to free Chase from his captors, but she pays a high price for her efforts. Wayne turns to Julia, while Palmer calls on Sherry for help against Milliken. Jack and Ramon make plans to get to Nina, in the hopes of intercepting the virus. Chloe's work at CTU is disrupted when she is forced to take care of her baby.

Undercover Agent Renee Walker confronts her painful past when attempting to broker a deal with a ruthless, but very well-connected German arms dealer. When CTU shifts its focus from the perilous circumstances surrounding Jack and Renee, lead analyst Dana Walsh comes up with a plan to quell her situation and Chloe O'Brian puts Arlo Glass in his place. As Jack and Renee’s undercover mission takes unexpected turns, the Hassan family turmoil has President Taylor reeling as the peace agreement is jeopardized.

As the terror threat continues, the Hassan family turmoil fans the flames of the increasingly urgent situation. When Jack closes in on a person of significant interest, a tense meeting between President Taylor and Omar Hassan takes an unexpected turn as the global security stakes are raised.

After Jack convinces Palmer he is not trying to kill him, they go over the "Operation Nightfall" file. The goal of the operation was killing a man named Victor Drazen, and a startling piece of information in the file convinces Jack and Palmer that they are both being targeted. Meanwhile, a scare at the clinic results in Teri and Kim being whisked away to a safe house.

Jack learns that one of the assassins, Alexis Mecir, is actually Victor Drazen's son and has become intimate with one of Palmer's aides. In an attempt to find the man ordering the assassinations, the aide agrees to plant a tracking device in Alexis' wallet. Back at the safe house, Teri and Kim discover their location is no longer secret or safe.

Three years have passed since the events of Day Two. A van deposits a dead body outside the LA Health Unit. The body is infected with a deadly virus. Tony, now in charge of CTU, learns that this is a blackmail tactic to get the US government to release a drug lord, Ramon Salazar, whom Jack has just brought down, before Salazar's brother releases the virus into LA. Jack and his new partner, Chase Edmunds, prepare to sign a deal with Salazar at the prison. Salazar delivers a mysterious warning to Jack before killing his lawyer. Palmer is alive and well, and has returned to LA for the first time since the attack three years ago. He is running for re-election and is preparing for an important debate with a rival senator. He is accompanied by his brother, who happens to be his chief of staff and his doctor, who also happens to be his girlfriend. A young boy, Kyle Singer, is seen examining a large, mysterious bag of white powder. He plans to deliver it to some dealers later that day, but he is being watched by Salazar's men. Kim now works at CTU and has been dating Chase for three months. Kim wants to tell her father, but Jack has a mysterious health problem that may make things more complicated.

Jack and Hector both search for Kyle, while Chase finds himself out of action at CTU. Wayne and Palmer argue over the implications of Anne's past, while Ramon takes out one of his opponents in a surprise move. Tony leads an operation to get Kyle, but tragedy strikes when Salazar's man gets there first.

Ramon holds Jack hostage as he flies to Mexico. Ramon plans to kill Jack, but Jack manages to hold him at bay until the plane lands. Ramon then learns that Jack and Hector are working together to break him out of prison. Gael is captured while trying to escape from CTU. Chappelle interrogates Gael but is interrupted by Tony, who claims that Gael is part of a bigger plan. Anne is given a chance to clear Palmer's name, while Chase heads for Mexico to rescue Jack.

Jack attempts to use Saunders' daughter as leverage to gain control of the virus, while Palmer must deal with the discontented press. Michelle gets the results of her test, while Adam finds that the virus has struck too close to home. Tony finds himself compromised when Saunders exploits his only weakness.

Jack and Tony clash as the time for the hostage exchange draws near. Keeler meets with Palmer and demands his resignation, while Wayne begins a secret operation against Sherry.

Jack's search takes him to the home of an old enemy, while a bomber slips into the White House.

Russian ire worries the White House, while the Chinese take on CTU, and the damaged circuit board is in surprising hands.

While lives remain on the line, an emotional Chloe copes with the declining conditions. With only a few hours left in Jack Bauer’s day, the situation worsens when the politicking inside the White House corners the divided administration.

For the first time in New York City, Jack Bauer is reluctantly drawn into action as President Allison Taylor negotiates plans for international security with Middle Eastern leader Omar Hassan. As the 8th day keeps unfolding, we learn that CTU, now upgraded and operated by M.B.A.-schooled Brian Hastings, still has Chloe O'Brian, but also expert analyst Dana Walsh and systems analyst Arlo Glass.

Four explosive hours after being unwillingly drawn back into action, Jack Bauer reteams with a risky Renee Walker to track some very dangerous leads. Meanwhile, back at CTU, a desperate Dana Walsh faces tense and untimely circumstances, and emotions escalate when President Taylor learns of a larger looming threat that jeopardizes the peace accord with President Hassan.

Despite averting the assassination attempt on foreign peacekeeping leader Omar Hassan, Jack Bauer's day intensifies when he is forced to go further undercover to secure the unsecured enriched nuclear materials. As international delegates reconvene at the United Nations, President Taylor's goodwill comes into question and CTU races against time to assist with the mission.

Moments after discovering his daughter, Kimberly, has snuck out of the house, Jack Bauer is called into work. As head of the CIA's Los Angeles Counter Terrorist Unit office he's told that an assassination attempt will be made within the next 24 hours on the life of presidential candidate David Palmer and it's up to his team of agents to keep Palmer alive. Meanwhile, Jack's wife, Teri, sets out to find their daughter.

Marwan decides to trade Jack for Behrooz in hopes of distracting CTU from his real objective. Tony and Michelle weigh the consequences of the trade, while Curtis reluctantly interrogates Behrooz in order to learn more about Marwan.

Four more "suitcase nukes" are out there, and Jack's only lead takes him to the home of his brother.