Understanding exposure continues to be a paramount challenge and critical element in successfully managing Superfund sites. The Superfund Basic Research Program, administered by the National Institute of Environmental Health Sciences, an institute of the National Institutes of Health, is committed to providing the nation's decision makers with better tools to identify the routes and effects of exposure and develop innovative technologies to reduce exposures. In this article, we demonstrate how the program contributes to understanding the exposure disease link, highlight the cutting-edge and practical nature of this very fundamental research program and discuss its approach to addressing these problems. We also identify several broad themes that are likely to direct the program's future research endeavors.