Obesity, diabetes, and other diet-related chronic diseases persist in American Indians at rates that are significantly higher than those in other ethnic minority populations. Environmental interventions to improve diet and increase physical activity have the potential to improve these health outcomes, but relatively little work has taken place in American Indian communities. We reviewed the experiences and findings of the following 3 case studies of intervention trials in American Indian communities: the Pathways trial, which was a school-based trial that focused on children; the Apache Healthy Stores program, which was a food-store program that focused on food preparers and shoppers; and the Zhiwaapenewin Akino'maagewin trial, which was a multiinstitutional trial for First Nations adults that worked with food stores, elementary schools, and health and social services agencies. All 3 trials showed mixed success. Important lessons were learned, including the need to focus on supply and demand, institutional and multilevel approaches, and the identification of institutional bases to sustain programs.