New technology for studying vascular activity in vivo has shown that the endothelium plays a critical role in the development of atherosclerosis. The healthy endothelium is a metabolically active tissue that exquisitely regulates vascular tone via release of the powerful vasodilator, nitric oxide. Endothelial integrity reduces cell adhesion, lipid deposition, and other early steps in atherogenesis. There is compelling evidence that endothelial function can be altered within hours of eating certain foods, further affirming the role of dietary factors in the prevention and progression of cardiovascular disease. This article reviews recent work on dietary factors (fatty acids, L-arginine, antioxidants, polyphenols, and folic acid) that alter vascular tone, and critically evaluates two noninvasive measures (flow-mediated dilation and total peripheral resistance) for use in dietary intervention trials.