SUMMARY OBJECTIVE: The majority of the mortality, morbidity, and disability in the United States and other developed countries is due to chronic diseases. These diseases could be prevented to a great extent with the elimination of four root causes: physical inactivity, poor nutrition, smoking, and hazardous drinking. The objective of this analysis was to determine whether efficacious risk factor prevention interventions exist and to examine the evidence that population-wide program implementation is justified. MATERIALS AND METHODS: We conducted a literature search for meta-analyses and systematic reviews of trials that tested interventions to increase physical activity, improve nutrition, reduce smoking and exposure to environmental tobacco smoke, and reduce hazardous drinking. RESULTS: We found that appropriately designed interventions can produce behavioral change for the four behaviors. Effective interventions included tailored fact-to-face counseling, phone counseling, and computerized tailored feedback. Computer-based health behavior assessment with feedback and education was documented to be an effective method of determining behavior, assessing participant interest in behavior change and delivering interventions. Some programs have documented reduced health care costs associated with intervention. CONCLUSIONS: Positive results to date suggest that further investments to improve the effectiveness and efficiency of chronic disease risk factor prevention programs are warranted. Widespread implementation of these programs could have a significant impact on chronic disease incidence rates and costs of health care.