The global obesity epidemic has been on the rise for four decades, yet sustained prevention efforts have barely begun. Quantitative models have provided key insights into the dynamics of this epidemic, allowing for the calculation of the impact of behaviors, interventions, and policies at multiple levels. Energy gap models have quantified the relationships between changes in energy intake and expenditure and weight change, highlighting the dominant role of increasing intake on obesity prevalence. While the evidence base for effective interventions is limited, several cost-effective policies are identified that governments should prioritize for implementation. Systems science provides a framework for organizing the complexity of forces driving the obesity epidemic and has important implications for policymakers. Multiple players, including governments, international organizations, the private sector, and civil society, need to contribute complementary actions in a coordinated approach. Priority actions include policies to improve the food and built environments, cross-cutting actions (such as leadership, health-in-all policies, and monitoring), and increased funding for prevention programs. Increased investment in population obesity monitoring would improve the accuracy of forecasts and evaluations. Embedding actions within existing systems in both health and non-health sectors can greatly increase impact and sustainability. The authors call for a sustained worldwide effort to monitor, prevent, and control obesity.The global obesity epidemic has been on the rise for four decades, yet sustained prevention efforts have barely begun. Quantitative models have provided key insights into the dynamics of this epidemic, allowing for the calculation of the impact of behaviors, interventions, and policies at multiple levels. Energy gap models have quantified the relationships between changes in energy intake and expenditure and weight change, highlighting the dominant role of increasing intake on obesity prevalence. While the evidence base for effective interventions is limited, several cost-effective policies are identified that governments should prioritize for implementation. Systems science provides a framework for organizing the complexity of forces driving the obesity epidemic and has important implications for policymakers. Multiple players, including governments, international organizations, the private sector, and civil society, need to contribute complementary actions in a coordinated approach. Priority actions include policies to improve the food and built environments, cross-cutting actions (such as leadership, health-in-all policies, and monitoring), and increased funding for prevention programs. Increased investment in population obesity monitoring would improve the accuracy of forecasts and evaluations. Embedding actions within existing systems in both health and non-health sectors can greatly increase impact and sustainability. The authors call for a sustained worldwide effort to monitor, prevent, and control obesity.