Edward "Eddie" Morra (Bradley Cooper) is a writer who lives in New York City and has recently been dumped by his girlfriend Lindy (Abbie Cornish) in addition to failing to meet the deadline to turn in his new book, which he hasn't started yet. One day, Eddie comes across Vernon Gant (Johnny Whitworth), the brother of his ex-wife, Melissa Gant (Anna Friel). Vernon is a drug dealer who offers Eddie a sample of a new drug, NZT-48, claiming it has the ability for humans to access 100% of the brain's power, as opposed to the normal 20%. Eddie accepts, and, much to his surprise, the drug does indeed work, allowing him to finish his book.
Eddie asks Vernon for more of the drug, and Vernon agrees, after Eddie runs a few errands for him. When Eddie returns to Vernon's apartment, he finds Vernon murdered and promptly calls the police. He quickly deduces that Vernon was probably killed by someone who wanted his stash of NZT and he searches Vernon's apartment for it. He finds the stash of NZT and a wad of cash and uses it to turn his life around. He abandons his writing career and starts trading stocks, borrowing capital from a Russian thug, Gennady. He becomes rich at an incredibly fast pace and is soon employed by the powerful businessman Carl Van Loon (Robert DeNiro). Eddie also gets back together with Lindy. Meanwhile, he feels that he is being followed by a man in a tan coat (Tomas Arana). He also starts using more and more NZT, causing side effects to occur—lost time, frenetic activity, and heart palpitations.
Eddie fails to accomplish a task assigned to him by Carl because of an NZT hangover, and fears he might even have killed a woman during some lost time. He is contacted by his ex-wife Melissa and learns that she had been an NZT addict and that withdrawal from the drug causes major health and mental problems, possibly always ultimately resulting in death. Eddie is warned by her to taper off the NZT before it's too late. When Gennady comes calling, he tries one of Eddie's pills. Gennady quickly realises the drug's effects, and threatens Eddie until he agrees to give him more NZT, which Eddie supplies. Eddie hires bodyguards to protect himself.
Eddie manages his consumption of the drug down to an acceptable level, and uses his fortune to hire a scientist to work on reverse engineering NZT, a process that could take years. He also once again assists Carl, this time on a big company merger deal with a rival businessman. Before the deal can take place, the rival falls ill, and Eddie understands that this illness must be due to withdrawal from NZT. Eddie understands that the man in the tan coat was working for this man, obviously trying to get his stash of NZT. As the business deal begins to unravel, Eddie's "powers" fade as he is overdue for his next dose of NZT, but he finds that his stash has been stolen. He locks himself in his apartment, but Gennady and his two henchmen show up, desperate for more NZT. A desperate Eddie, going through NZT withdrawal, figures there is no way out of this predicament, except to kill himself, because he won't allow Gennady and his thugs to get him. Eddie stands on the edge of his balcony contemplating suicide, but he changes his mind when he realizes he might still have an NZT pill lying around somewhere. He heads back in to search for his last NZT, while Gennady and his thugs cut open his fortress-like door with a circular saw. He finds the pill, but drops it in panic when Gennady's posse finally breaks in, and it ends up falling down an air vent. Gennady and his two henchmen intend to torture and kill him to get the NZT. Although Eddie is out of NZT, he realizes he can still get a high if he can kill Gennady and drink his blood. The plan works, he kills his attackers, then tracks down his stolen NZT and recovers it when the businessman who had hired the man in the trenchcoat dies, making the drug of no use to the man in the trenchcoat.
A year later, Eddie has had his book published, Illuminating the Dark Fields (the real title of the novel on which the film is based). He is also running for the United States Senate and is looked upon as a potential candidate for the United States Presidency. In the midst of his Senate campaign, Carl approaches Eddie with the revelation that he bought the company that secretly makes NZT and the back room NZT lab Eddie was financing has been shut down. Carl offers him an unlimited supply of NZT; however, Eddie must use his political position to push Carl's agenda in return. Eddie refuses the offer, informing Carl that he no longer needs the drug. His prolonged use, plus a modified version by his private scientist that got rid of the kinks, allowed him to wean off it and it altered his brain chemistry to the point where he is practically superhuman. A demonstration of this is enough for Carl to retreat. The film ends with Eddie in a Chinese restaurant, about to have lunch with Lindy, comfortably joking with the waiter in Mandarin or Cantonese (one of several languages he easily picks up in the movie), with clearly no intention of stopping his rise to the top just yet.
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