The most recent estimates classify more than 35% of U.S. adults as obese. Obesity has been linked to increased risk of diseases such as hypertension, diabetes mellitus, kidney disease, and cancer; decreased life expectancy; and increased costs. Healthy People 2020 identified preventing weight gain and the development of obesity as a priority area, specifically to increase the prevalence of a healthy weight among adults from 31% to 34% and reduce the prevalence of obesity among adults to less than 30%. Despite this goal, we know of no treatment guidelines for the prevention of weight gain or maintenance of weight. Stakeholders identified combination interventions as the priority for future research. They stated that multiple factors contribute to weight gain and felt that interventions would need to address multiple factors, which would likely require multiple components. Stakeholders selected interventions that combined either self-management, diet, and exercise or self-management, diet, exercise, and environmental alterations as the two highest priority combinations of interventions. The two highest priority comparisons of interest were self-management and diet versus either self-management and exercise or self-management, diet, and exercise. Stakeholders identified the primary outcome of interest for all interventions as weight gain prevention. Because no standard definition of weight maintenance exists, all stakeholders agreed that the field of weight gain prevention would benefit from the establishment of a standard definition. This definition would ensure that future studies of weight gain prevention have an adequate duration of follow up to confirm weight maintenance and also improve comparability of results across studies. Stakeholders identified two priority secondary outcomes that should be assessed in future interventions. First, they felt that adherence was a critical intermediate outcome in evaluating the efficacy of the intervention and identifying subgroups that may be most responsive to a particular intervention. Second, they identified weight-related clinical conditions, including cardiovascular disease and diabetes, as important secondary outcomes. Their justification was that interventions that not only prevent weight gain but also prevent or reduce the incidence of weight-related diseases would have a significant public health impact. Future research questions: To prevent weight gain in all adults, what is the comparative effectiveness of adding physical activity versus not adding physical activity to a work-based self-management and diet intervention? To prevent weight gain in all adults, what is the comparative effectiveness of adding physical activity versus not adding physical activity to a home-based self-management and diet intervention? To prevent weight gain in all adults, what is the effectiveness of a work-based self-management and physical activity intervention versus a self-management and diet intervention? To prevent weight gain in all adults, what is the effectiveness of a home-based self-management and physical activity intervention compared with a self-management and diet intervention? To prevent weight gain in overweight adults, what is the comparative effectiveness of adding physical activity versus not adding physical activity to a home-based self-management and diet intervention? To prevent weight gain in overweight adults, what is the effectiveness of a home-based self-management and physical activity intervention compared with a self-management and diet intervention? To prevent weight gain in young adults, what is the comparative effectiveness of adding physical activity versus not adding physical activity to a home-based self-management and diet intervention? What is a clinically meaningful definition of weight maintenance among adults, expressed as both weight (kg) and body mass index (kg/m2), that can be used as the standard across studies of weight gain prevention?