Nikita, a girl living on the streets, is wrongly accused of a murder she did not commit and sentenced to life in prison. After the government arranges to fake her suicide, Nikita wakes up at Section One, a top-secret agency that aims to train her to become an anti-terrorist operative. Nikita wants to resist, but in order to stay alive, she has no choice, but to comply with their plans.

When an international arms smuggler steals a canister of deadly nerve gas, Nikita and Michael pose as a married mercenary couple in order to infiltrate his compound. However, when the gas is discovered wired to a bomb in a crowded train station, Nikita must put her life on the line to defuse it.

Section was informed that the water of the city would be polluted if the United Coalitions needs weren't met. Gregor Kessler, the one with many aliases and disguises, steals the Cobalt 60. Kessler was offered money to get the Cobalt 60, reported by a spy of Section. Gregor dresses up as an aged lady to get through South American Customs. Kessler manages to capture the Cobalt 60, but Madeline confronts him. Some how, he knows about her past and starts intimidating her. Section takes Kessler's daughter in hope to retreive the Cobalt 60. This doesn't work for him because he kills her, so Section can't hurt her. Meanwhile, Nikita finds out more about Madeline's past & what she did to her sister. Madeline never wanted anyone to know about it. Kessler now wants Madeline, Section doesn't want her to go by herself, so they stand by in a nearby distance. Madeline falls into a hole where Gregor is. He grips her up by the neck, but she breaks free. It wasn't really her, it was Michael dressed up

With Michael's help, Nikita survived the destruction of a Freedom League hideout in the first season's final episode. Since then, she has been on the run from Section One. While working as a waitress, Nikita is captured by the Freedom League and used as bait to lure Section One into a trap. During a raid by a Section team led by Michael, Nikita saves Michael's life and they manage to escape together. Later, on an abandoned ship, Nikita and Michael share a night of passion. However, Michael's lies about Nikita's whereabouts are in danger of being exposed.

Nikita continues to show evidence of the "reprogramming," including ordering the elimination of a captured Section operative and endangering the lives of children during a mission, and taking part in the beatings of a captive. Michael is determined to reverse Nikita's reprogramming, and he soon determines that the former Section operative who came up with the "reprogramming" process, Ross Gelman, may be the key. Meanwhile, Operations couldn't be more proud of the "new" Nikita, but Madeline is still worried. Eventually, Operations concludes that Michael's attempts at restoring Nikita have gone too far, and takes extreme measures.

Michael discovers that Adrian's mind is not blank as he thought it is. Together they try to save George from Operations and Madeline's attempt to assassinate him. Meanwhile, Michael kidnaps Nikita in a futile effort to reason with her.

After Substation three is destroyed by self-destruct, Section One investigates and finds a trace to Red Cell. What they also discover is that Red Cell has been taking similar blows. Operations decides to become allies and for each other to send top-notch agents. Operations sends Madeline, though Operations is willing to risk her.

Nikita is sent back to Section One to destroy a new terrorist threat that only she can deal with which is a summit meeting of representatives from several terrorist groups. She is teamed up with a new level 5 operative, Marco O'Brien. O'Brien was the police officer recruited four years earlier because of a mistake Nikita made, a fact that O'Brien has not forgotten. Nikita finds that besides the terrorists, she must deal with O'Brien & the hostility of much of Section personnel because of her role in Center's evaluation of Section.