The deleterious consequences of environmentally associated diseases are expressed differentially by income, race, and geography. Scientists are just beginning to understand the consequences of environmental exposures under conditions of poverty, marginalization, and geographic isolation. In this context, we developed the TERRA (translational environmental research in rural areas) framework to explicate environmental health risks experienced by the rural poor. Central to the TERRA framework is the premise that risks exist within physical-spatial, economic-resources, and cultural-ideologic contexts. In the face of scientific and political uncertainty, a precautionary risk reduction approach has the greatest potential to protect health. Conceptual and technical advances will both be needed to achieve environmental justice.