Cigarette smoking is the most important modifiable risk factor for premature mortality. Many common and serious diseases, including coronary artery disease, chronic obstructive lung disease, stroke, and cancer, are strongly linked to cigarette smoking. Smoking cessation is difficult due to nicotine addiction and withdrawal symptoms. Comprehensive programs for tobacco control can substantially reduce the frequency of tobacco use. Physicians can improve screening and increase cessation rates by asking patients about tobacco use at every office visit. The spectrum of available smoking cessation interventions ranges from simple advice to intensive behavioral support and pharmacological treatment. Medications currently approved by the US Food and Drug Administration for smoking cessation include nicotine replacement therapy (patch, gum, lozenge, inhaler, and nasal spray), bupropion, and varenicline. Nortriptyline and clonidine have been used in patients who do not tolerate first-line agents. New drug therapies, such as nicotine vaccines, are being developed. The US Public Health Service Guideline, published in 2008, recommends a combination of behavioral support and pharmacologic therapy. In summary, smoking cessation should be based on a patient's coexisting medical conditions, level of smoking, compliance, previous experience with cessation agents, and the cost of therapy.