Varenicline is a selective alpha(4)beta(2) nicotinic acetylcholine receptor partial agonist and the first non-nicotine-containing medication developed with the sole purpose of treating nicotine addiction. To date, four published clinical trials have demonstrated the efficacy and safety of varenicline for smoking cessation in healthy adults who were ready to make a quit attempt. One additional trial found that extended use of varenicline effectively reduced relapse to smoking. One trial to date published as a poster documented the 1-year safety of the drug. Varenicline was more efficacious than bupropion 24 weeks after randomization to a 12-week treatment course and 1 year after randomization in an identical trial. It has no contraindications except hypersensitivity and is well tolerated. This article reviews the available information on varenicline and discusses its clinical use.