Changes in endothelial cell physiology are now an accepted component of inflammatory and atherosclerotic vascular disease. This communication will review the scientific and clinical evidence that supports this statement, which may be demonstrated by in vivo arterial manipulations or by measuring plasma levels of endothelial cell-specific products. The former invasive approach has provided useful insights into the pharmacology of blood flow and blood pressure regulation whilst the latter has provided epidemiological evidence that endothelial cell injury can lead to an increased risk of morbidity and mortality. In addition, studies based on both techniques have demonstrated that treatment or reversal of the risk factors for atherosclerosis can be beneficial to the endothelium, validating the theory that the endothelium is the prime target for the disease process.