Increases in the prevalence of overweight and obesity are a function of chronic, population-level energy imbalance, whereby energy intakes exceed energy expenditures. Although sometimes viewed in isolation, energy intakes and expenditures in fact exist in a dynamic interplay: energy intakes may influence energy expenditures and vice versa. Obesogenic environments that promote positive energy balance play a central role in the obesity epidemic, and reducing obesity prevalence will require re-engineering environments to promote both healthy eating and physical activity. There may be untapped synergies in addressing both sides of the energy balance equation in environmentally focused obesity interventions, yet food/beverage and physical activity environments are often addressed separately. The field needs design, evaluation, and analytic methods that support this approach. This paper provides a rationale for an energy balance approach and reviews and describes research and practitioner work that has taken this approach to obesity prevention at the environmental and policy levels. Future directions in research, practice, and policy include moving obesity prevention toward a systems approach that brings both nutrition and physical activity into interdisciplinary training, funding mechanisms, and clinical and policy recommendations/guidelines.