Cigarette smoking is a major preventable cause of morbidity and mortality. It is the major risk factor for chronic obstructive pulmonary disease in the developed world. Smoking is a chronic relapsing disease. Optimal treatment includes nonpharmacologic support, together with pharmacotherapy. All clinicians should be comfortable with the use of nicotine replacement therapy, bupropion, and varenicline. Second-line therapies can be used by those familiar with their use. Effective use of these medications requires their integration into an effective management plan, which is likely to be a long-term undertaking, involving several cycles of remission and relapse.