The purpose of this study was to conduct a systematic review of the scientific literature to identify and assess the evidence for the efficacy of three antioxidants, vitamin E, vitamin C, and coenzyme Q10, for the prevention and treatment of cardiovascular disease (CVD) or modification of known risk factors for CVD. A broad search found sufficient literature to perform a detailed review of the use of these antioxidants for CVD. CVD, defined as coronary artery disease, hypertensive heart disease, congestive heart failure, peripheral vascular disease, and atherosclerosis, including cerebral artery disease and strokes, is the leading cause of death in the United States. Modification of the major risk factors for CVD (diabetes mellitus, hypertension, hypercholesterolemia, and smoking) has been associated with a decreased risk of CVD. Thus, identification of interventions that treat CVD or modify the underlying risk factors would be of great interest. Observational data suggest that fruit and vegetable consumption lowered the risk of developing CVD. It has been postulated that the antioxidant component of fruits and vegetables accounted for the observed protection. Decreased risk of cardiovascular death has been associated with higher blood levels of vitamin C and coenzyme Q10. In addition, vitamin C, vitamin E, and coenzyme Q10 have demonstrated antioxidant effects, including beneficial effects on oxidation of low-density lipoprotein. There is evidence that these vitamins affect other risk factors for CVD such as hypertension. Vitamin E may also reduce coronary artery blockage by decreasing blood platelet aggregation. Thus, it was reasonable to expect that supplementation with these antioxidants would decrease the risk of developing CVD. Large numbers of people are taking antioxidants with the expectation that they will prevent disease.