Tobacco use is one of the leading preventable causes of death in developed countries. Adoption of approaches that have demonstrated efficacy to improve the treatment of tobacco dependence are critical to reduce the health consequences of tobacco use. We summarize the latest epidemiologic data on tobacco use, the mechanisms that underlie tobacco dependence, and advances in pharmacotherapy and nonpharmacologic interventions available for the treatment of tobacco dependence. Specifically, we discuss the use of nicotine replacement therapy, bupropion and varenicline in primary care settings.