Endothelial dysfunction is a well documented early phenomenon in atherosclerosis. Because it may precede structural changes and clinical manifestations, major research efforts have focused on the detection of endothelial dysfunction in humans. The utility of such tests in clinical practice critically depends on the proof of their prognostic value, their safety and reproducibility. First data supporting the prognostic impact of endothelial function have come from studies using intracoronary infusion of acetylcholine, a test clearly too invasive to be performed in asymptomatic subjects. Therefore, non-invasive techniques such as flow-mediated vasodilation of the brachial artery and strain-gauge venous plethysmography of the forearm have been developed. Numerous studies in a variety of patient populations have been performed to evaluate the prognostic value of these methods. This review summarizes the current status of endothelial dysfunction as an early parameter of atherosclerosis and its potential use in the clinical arena. The value of endothelial function as a surrogate endpoint in cardiovascular studies is critically reviewed.