After Dr. Ellen Sanders, a prominent Washington D.C. surgeon, is handpicked to operate on the President of the United States, rogue FBI agent Duncan Carlisle and armed intruders suddenly take her and her family hostage. Scared and bewildered, Ellen soon learns the reason: unless she assassinates the President during surgery, her captors will kill them all.
When Ellen's sister, Lauren, shows up unexpectedly at their house intending to stay, Duncan forces Ellen to get rid of her without making it look suspicious. Meanwhile, when the secret service calls Ellen in for questioning again, she must play it cool when Duncan is there to help do the questioning.
Ellen and Brian agree that they need to take down Duncan to have any chance of escaping, so she sneaks away to see a man who has previously helped her solve problems. However, unbeknownst to her, this man has ties to Duncan. Meanwhile, Archer's accomplice plans to reveal to the Assistant District Attorney information about a murder Archer committed.
Ellen must decide whether to save Duncan’s life, and later decides to confront his wife. Meanwhile, Creasy meets with Vanessa and Colonel Blair after the President informs them that he wants to expose the details of Operation Total Information, a government surveillance program that allowed intelligence agencies to spy on U.S. citizens.
After a member of the President's staff is murdered, Ellen urges Duncan to back out of the assassination plot, while other members of the President's staff take matters into their own hands. Meanwhile, after scouring Nina's medical records, Ellen finds someone who might be a viable bone marrow donor.
It’s the day of the President’s surgery and the various plots are in motion. Just before the surgery begins, Ellen is cornered by the First Lady, who finally sees through Ellen’s lies about her husband’s condition and forces her to tell the truth about the assassination plot. Ellen spills the secrets Kincaid has been keeping from his wife and she agrees to help get the bone marrow out of the hospital. Blair’s squad of hired terrorists move into position after passing themselves off as Secret Service agents, and they launch their diversionary attack just after Ellen nicks an artery during surgery. Once Ellen is alone with the President and Logan, she gives Logan a sedative, extracts the bone marrow, and prevents the President from bleeding out on the operating table. Once the terrorist threat is subdued, Ellen takes the bone marrow to Nina, who accepts it and apologizes for everything Duncan did to her family. Meanwhile, Duncan schemes with Vanessa to outwit Blair and free his family. He corners Blair at gunpoint at a fundraising banquet and demands that Blair’s men release Nina and Sawyer. Once they’ve been released, Blair lashes out, forcing Duncan to shoot and kill him. Duncan then confronts Archer, who has captured the rest of the Sanders family and demands payment for his services. The two battle in a brutal fistfight with Archer coming out on top, but Kramer arrives just in time to save Duncan and kill Archer. Duncan then reunites with Nina and Sawyer briefly, saying goodbye before turning himself in to the police for his actions.