The vascular endothelium is the primary site of dysfunction in many diseases, particularly cardiovascular disease. A variety of risk factors, including smoking, hypercholesterolemia, hyperhomocysteinemia, hypertension, and diabetes mellitus, adversely affect endothelial function. Emerging evidence suggests an important role of dietary factors in modulating endothelial function. In particular, n-3 fatty acids, antioxidant vitamins (especially vitamins E and C), folic acid, and L-arginine appear to have beneficial effects on vascular endothelial function, either by decreasing endothelial activation or by improving endothelium-dependent vasodilation in patients at high risk of cardiovascular disease as well as in healthy subjects. These effects may serve as one potential mechanism through which these nutrients reduce the risk of cardiovascular disease, as observed in epidemiologic studies and several clinical trials. This article reviews clinical and experimental evidence regarding the role of these nutrients in modulating endothelial function and their potential to prevent cardiovascular disease.