The current dialogue on reform of the US health care system is conspicuous for the absence of an epidemiologically driven framework that focuses on the prevention of disease. Review of epidemiologic and demographic trends in the American population illustrates that if reform fails to advance the point of intervention to earlier in the course of disease, a restructured health care system is unlikely to provide comprehensive services with universal access. Sustainable reform warrants a preventive orientation and greater balance between primary, secondary, and tertiary levels of intervention. This report considers trends that may render economically driven reform rapidly obsolete, as well as cultural obstacles to the development of a prevention ethos in US health care and culture. The economy of prevention is described in the context of leading causes of US morbidity and mortality. Elements of a national disease prevention strategy are considered that include changes in mechanisms of physician/provider reimbursement, the orientation of private-sector biotechnology/health care research, tertiary medical centers and academia, and improved abilities to reduce the concentration of preventable morbidity and mortality in high-risk communities and to use epidemiology in formulating health policy.