Cigarette smoking remains an important risk factor for premature cardiovascular disease and its many complications. There are clear benefits from treating tobacco dependence on the rate of clinical outcomes. In addition to behavioral therapies, various pharmacologic strategies have been developed to help achieve this goal. First-line therapies include nicotine replacement, bupropion and varenicline, a partial nicotine antagonist. 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, anti-anxiety drugs, nicotinic receptor antagonists (e.g. mecamylamine) and glucose tablets. Various approaches under investigation include inhibitors of the hepatic P450 enzyme (e.g. methoxsalen), cannabinoid-1 receptor antagonists (e.g. rimonabant), and nicotine vaccines.