Endothelial dysfunction is a key event in cardiovascular disease. Measurement of endothelial dysfunction in vivo presents a major challenge, but has important implications since it may identify the clinical need for therapeutic intervention, specifically in primary prevention. Several biological markers have been used as indicators of endothelial dysfunction. The soluble adhesion molecules sICAM-1 and sVCAM-1 lack specificity and are increased in inflammatory processes. Both markers are increased in coronary artery disease. sICAM-1 level predicts the risk for cardiovascular disease or diabetes mellitus in healthy individuals. sE-selectin is specific for the endothelium and is increased in coronary artery disease and diabetes mellitus. sE-selectin is also associated with diabetic risk. The endothelium-specific marker, soluble thrombomodulin, is associated with severity of coronary artery disease, stroke or peripheral occlusive arterial disease and is not increased in healthy or asymptomatic subjects. Interestingly, thrombomodulin decreases during treatment of hypercholesterolemia or hyperhomocysteinemia. In contrast, von Willebrand factor is the best endothelial biomarker and predicts risk for ischemic heart disease or stroke.