Cigarette smoking remains an important risk factor for premature cardiovascular disease and its complications. There are clear benefits of cigarette smoking cessation on the rate of clinical outcomes, and in addition to behavioral therapies, various pharmacologic strategies have been developed to help achieve this goal. First-line therapies include nicotine replacement and/or bupropion. Second-line treatments include clonidine and nortriptyline. Additional treatment strategies, with less proven efficacy, include monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, opioid receptor antagonists, bromocriptine, antianxiety drugs, nicotinic receptor antagonists (eg, mecamylamine), and glucose tablets. Various approaches under investigation include the use of partial nicotine agonists (eg, varenicline), inhibitors of the hepatic P-450 enzyme (eg, methoxsalen), cannaboid-1 receptor antagonists (eg, rimonabant), and nicotine vaccines.