Tobacco smoking is the leading cause of preventable death in the United States, and its harms are well established. Physicians have more evidence-based resources than ever before to effectively treat smoking, including new uses and combinations of U.S. Food and Drug Administration-approved pharmacotherapies and expanded community programs. In addition, electronic nicotine delivery systems are potential treatment tools, but their safety and efficacy need to be established. Finally, high-priority groups, such as persons with cancer diagnoses or hospitalized patients, may benefit from particular attention to their tobacco use.