Decreased arterial compliance (increased stiffness) correlates with cardiovascular events, possibly due to increased cardiac afterload caused by more rapidly reflected pulse waves. Endothelium-derived mediators regulate vascular tone and structure, both of which can markedly influence arterial stiffness. Thus, increased arterial stiffness may be a mechanism by which endothelial dysfunction predisposes to complications of atherosclerosis. Conversely, therapeutic manipulation of endothelial mediators could reduce arterial stiffness and cardiovascular events. Techniques have been developed that use measures of arterial stiffness as an index of endothelial dilator function; these may provide unique prognostic information to identify high-risk subjects.