Following a brief review of the etiology and prevalence of tobacco use and data on the effectiveness of prevention and cessation interventions, recommendations for a research agenda are outlined. It is suggested that research on youth tobacco initiation and cessation be given highest priority because of rising prevalence rates, fundamental social importance, and the widespread support for such efforts. Policy and community approaches to deterring youth tobacco use deserve particular attention. Adult intervention research should focus on health care settings and include factors that both help and hinder adoption and routine implementation of tobacco interventions by clinicians. Developing and evaluating practical ways of using nicotine replacement therapies or other pharmacological therapies in primary care are also of importance. Media interventions that segment the smoking population by age, ethnicity, and developmental milestones should be encouraged. Three approaches could profit from working conferences of investigators and other interested parties to review the data and suggest research directions: worksite interventions, interventions with ethnic populations, and matching or tailoring interventions to specified characteristics of smokers. The importance of devoting considerable resources to investigator-initiated contrasted with sponsor-directed research is discussed.