Electronic nicotine delivery systems (ENDS), which include electronic cigarettes, or e-cigarettes, are growing in popularity, but their safety and efficacy as a smoking cessation aid are not well understood. Some argue that they have the potential to reduce tobacco-related morbidity and mortality and could be a useful tool for reducing tobacco-related harm. Others express concern that the health effects of ENDS use are unknown, that they may appeal to young people, and that they may encourage dual use of ENDS and traditional tobacco products. Although ENDS are a new and unregulated product, the U.S. Food and Drug Administration has proposed regulations that would deem ENDS to be subject to the Family Smoking Prevention and Tobacco Control Act, which regulates cigarettes and other tobacco products. In this position paper, the American College of Physicians offers policy recommendations on ENDS regulation and oversight, taxation, flavorings, promotion and marketing, indoor and public use, and research. This paper is not intended to offer clinical guidance or serve as an exhaustive literature review of existing ENDS-related evidence but to help direct the College, policymakers, and regulators on how to address these products.