Cigarette smoking represents the most important source of preventable morbidity and premature mortality worldwide. Approximately 100 million deaths were caused by tobacco use in the 20th century. There are >1 billion smokers worldwide, and globally the use of tobacco products is increasing, with the epidemic shifting to the developing world. Tobacco dependence is a chronic condition that often requires repeated intervention for success. Just informing a patient about health risks, although necessary, is usually not sufficient for a decision to change. Smokers should be provided with counseling when attempting to quit. Pharmacologic smoking cessation aids are recommended for all smokers who are trying to quit, unless contraindicated. Evidence-based guidelines recommend nicotine replacement therapy, bupropion SR, and varenicline as effective alternatives for smoking cessation therapy, especially when combined with behavioral interventions. Combination pharmacotherapy is indicated for highly nicotine-dependent smokers, patients who have failed with monotherapy, and patients with breakthrough cravings. An additional form of nicotine replacement therapy or an addition of a non-nicotine replacement therapy oral medication (bupropion or varenicline) may be helpful. The rate of successful smoking cessation at 1 year is 3% to 5% when the patient simply tries to stop, 7% to 16% if the smoker undergoes behavioral intervention, and up to 24% when receiving pharmacological treatment and behavioral support.