Prevention of disease and disability and preservation of health are compelling strategies that are endorsed by the public, health care providers, and researchers. Despite this general acceptance of the concept, the "devil is in the details." What can and should be recommended with confidence to the public and health care providers regarding prevention and how can these recommendations be implemented? Prevention programs should be based on durable evidence of efficacy and should assure that the benefits of interventions and changes exceed the risks. The latter is particularly important for population-based primary prevention because many are influenced but fewer may benefit. Prevention research must provide the evidence of benefit and risk. The responsibility of the National Institutes of Health (NIH) is to develop the scientific basis for prevention and to train prevention scientists who are responsible for creating this science base. The interpretation and dissemination of information from research studies are important and necessary aspects to assure translation of the science into personal and public health practices. The components of prevention research are investigation of the factors that place individuals and groups at risk of disease and disability; trials of the interventions that can modify this risk; and testing the approaches that can effectively implement beneficial changes. NIH is committed to addressing these endeavors, and its individual Institutes and Centers support a broad portfolio of prevention research. This paper will provide an overview of NIH support, the functional relationships of prevention research within NIH, and background information that can be useful to those interested in research.