Despite 2 decades of effort by the public health community to combat obesity, obesity rates in the United States continue to rise. This lack of progress raises fundamental questions about the adequacy of our current approaches. Although the causes of population-wide obesity are multifactorial, attention to food systems as potential drivers of obesity has been prominent. However, the relationships between broader food systems and obesity are not always well understood. Our efforts to address obesity can be advanced and improved by the use of systems approaches that consider outcomes of the interconnected global food system, including undernutrition, climate change, the environmental sustainability of agriculture, and other social and economic concerns. By implementing innovative local and state programs, taking new approaches to overcome political obstacles to effect policy, and reconceptualizing research needs, we can improve obesity prevention efforts that target the food systems, maximize positive outcomes, and minimize adverse consequences. We recommend strengthening innovative local policies and programs, particularly those that involve community members in identifying problems and potential solutions and that embrace a broad set of goals beyond making eating patterns healthier. We also recommend undertaking interdisciplinary research projects that go beyond testing targeted interventions in specific populations and aim to build an understanding of the broader social, political, and economic context.