The RTI International University of North Carolina at Chapel Hill Evidence-based Practice Center (RTI UNC EPC) conducted a systematic review of the literature on issues of tobacco use, prevention, cessation, and control on behalf of the National Institutes of Health (NIH), Office of Medical Applications of Research (OMAR), through the Agency for Healthcare Research and Quality (AHRQ). OMAR commissioned this review to summarize the available literature, frame the discussions regarding benefits and harms, and highlight the limitations of the entire evidence base for a State-of-the-Science (SOS) conference in June 2006. We synthesized existing literature on five main research issues needed to make progress toward public health gains worldwide. Specific substantive key questions (KQs) were: 1. What are the effective population- and community-based interventions to prevent tobacco use in diverse populations of adolescents and young adults? 2. What are effective strategies for increasing consumer demand among diverse populations for and use of proven individually oriented cessation treatments? 3. What are effective strategies for increasing implementation of proven population-level tobacco use cessation strategies, particularly by health care systems and communities? 4. What effect does smokeless tobacco product marketing and use have on population harm from tobacco use? 5. What is the effectiveness of prevention and of cessation interventions in populations with co-occurring morbidities and risk behaviors?"