Two things are very clear to physicians and smokers alike: Smoking is bad for your health, and it is devilishly hard to quit (1–2). Not surprisingly, therefore, many clinicians are pessimistic, even cynical, about treating smokers. “Why should I spend my limited time on this problem, when I know I am doomed to fail?” Actually, the rejoinders to this view—that smoking rates are at a historic low, that ex-smokers now outnumber current smokers, and that over 70% of smokers want to quit—are compelling. Physicians and smokers should also welcome the news that the FDA has approved a new drug, varenicline, for smoking cessation treatment. Varenicline, a partial nicotine agonist, has become the third pharmacologic agent approved by the FDA, following nicotine replacement therapy (currently available as patches, gum, lozenges, nasal spray, and an inhaler) and the psychoactive drug bupropion, approved in 1997 (3). Thus, after almost a decade, the FDA has had an opportunity to approve a new class of drug to treat the most important preventable health risk.