Research on smoking has increased in the past several years, and many new therapeutic modalities have been developed. Primary intervention for smoking cessation begins with systematic identification of smokers and a formal diagnosis of nicotine dependence. Providing self-help brochures without clinical advice has marginal efficacy, but these can be useful as an adjunct to clinician intervention. Several large studies have shown that physician advice alone can lead to quit rates of up to 10%, and follow-up for patients trying to quit can double cessation rates. Behavioral therapy alone has demonstrated cessation rates of approximately 20% for those willing to participate. Drug therapy remains the most attractive method of smoking cessation for many patients. The standard approach has been nicotine substitution using one of the four forms of nicotine replacement (gum, patches, nasal spray, inhaler) currently available. The efficacy of nicotine replacement products is similar, with each agent providing a doubling of the cessation rate. Thus, the choice of agent depends on patient factors and preference. Bupropion is the first nonnicotine-containing agent approved for smoking cessation, with cessation rates ranging from 10.5 to 24.4%, depending on dose. One-year follow-up suggests a continued benefit with this agent. The combination of bupropion and transdermal nicotine has also been shown to be effective for smoking cessation in clinical trials. Effective approaches to smoking cessation should combine identification of smokers, provision of advice at each visit, and widespread availability of treatment.