The number one cause of preventable disease, disability, and death in the United States is tobacco use. According to data from the National Health Interview Survey, 18.7% of US adults (46 million people) currently use a tobacco product. Smoking causes lung, laryngeal, hepatocellular, and colorectal cancers and possibly breast cancer. Nicotine is the highly addictive component of tobacco that releases dopamine when it binds to alpha-4 beta-2 nicotinic acetylcholine receptors in the brain. This produces reward sensations that become associated with specific behaviors and relieves stress and negative emotions. Public policy changes, behavioral interventions, and pharmacologic approaches have been shown to reduce tobacco use. Combining behavior therapy with pharmacotherapy increases cessation rates. The US Food and Drug Administration has approved five nicotine replacement therapies and two no-nicotine oral medications to assist with smoking cessation. Medications are categorized as controllers or relievers based on their pharmacokinetics. Nicotine replacement therapy delivers lower amounts of nicotine and needs to be titrated to alleviate patient cravings. Varenicline is a selective partial agonist at the alpha-4 beta-2 nicotinic acetylcholine receptor and is recommended over bupropion for smoking cessation.