Obesity is a major influence on the development and course of cardiovascular diseases and affects physical and social functioning and quality of life. The importance of effective interventions to reduce obesity and related health risks has increased in recent decades because the number of adults and children who are obese has reached epidemic proportions. To prevent the development of overweight and obesity throughout the life course, population-based strategies that improve social and physical environmental contexts for healthful eating and physical activity are essential. Population-based approaches to obesity prevention are complementary to clinical preventive strategies and also to treatment programs for those who are already obese. This American Heart Association scientific statement aims: 1) to raise awareness of the importance of undertaking population-based initiatives specifically geared to the prevention of excess weight gain in adults and children; 2) to describe considerations for undertaking obesity prevention overall and in key risk subgroups; 3) to differentiate environmental and policy approaches to obesity prevention from those used in clinical prevention and obesity treatment; 4) to identify potential targets of environmental and policy change using an ecological model that includes multiple layers of influences on eating and physical activity across multiple societal sectors; and 5) to highlight the spectrum of potentially relevant interventions and the nature of evidence needed to inform population-based approaches. The evidence-based experience for population-wide approaches to obesity prevention is highlighted.