With the dramatic increases in cost and complexity of medical treatment over the past few decades, the public has emphasized the need to increase efforts aimed at the primary prevention of major causes of illness and death. Screening, early detection, and preventive measures have become attractive alternatives to heroic treatment efforts that exhaust huge resources on the late stages of disease. A large number of research projects have demonstrated substantial public health benefits from preventive measures. While much more prevention research is needed, it is important to bear in mind that the answers to promising research questions are limited by a shortage of funding. The costly nature of prevention research in particular is a roadblock to funding. Due to the current organization of the National Institutes of Health, research in prevention often receives low priority. It is also increasingly apparent that coordination of the national research agenda for disease prevention needs to be better structured. This paper highlights a number of issues that need to be addressed in order to strengthen the prevention research program.