Mounting evidence suggests physical and mental health problems relate to the built environment, including human-modified places such as homes, schools, workplaces, parks, industrial areas, farms, roads and highways. The public health relevance of the built environment requires examination. Preliminary research demonstrates the health benefits of sustainable communities. However, the impact of mediating and moderating factors within the built environment on health must be explored further. Given the complexity of the built environment, understanding its influence on human health requires a community-based, multilevel, interdisciplinary research approach. The authors offer recommendations, based upon a recent conference sponsored by the National Institute of Environmental Health Sciences (NIEHS), for research and policy approaches, and suggest interagency research alliances for greater public health impact.