The endothelium is located at a strategic position within the vessel wall, being directly exposed to mechanical forces exerted by the blood, and to hormones and noxious substances. The endothelium (an autocrine, paracrine and endocrine organ) is a key player in regulation of vascular tone, thrombogenesis, inflammation and vessel growth. A crucial mediator of proper function of the endothelium is nitric oxide and its bioavailability. Cardiovascular risk factors such as dyslipidaemia, hypertension, diabetes and smoking result in a decreased nitric oxide bioavailability and enhance production of endothelial vasoconstrictors, such as endothelin-1 and oxygen free radicals. Endothelial dysfunction is the key step in atherogenesis and has been shown to predict clinical outcome, Hence, novel treatments that are aimed at improving endothelial function, such as statins and blockers of the renin-angiotensin system, are of particular clinical importance. (C) 2002 The European Society of Cardiology.