Endothelial cells that line the internal surface of the vasculature are a major regulator of vascular tone, inflammation, coagulation and platelet function. Endothelium exerts its effect by synthetize, metabolize and release numerous substances that regulates vascular homeostasis including endothelial derived hyperpolarizing factor, prostacyclin, thromboxane A2, kinins, adrenomedullin, angiotensin II, endothelin and nitric oxide. Endothelial dysfunction occurs when there is a disturbance of vascular homeostatic mechanism and impairment of endothelial derived vasorelaxation. Among the several pathomechanisms that are responsible for the endothelial dysfunction, oxidative stress, inflammation and the reduction of nitric oxide bioavailability are the most important mechanisms. A Varity of risk factors play a critical role in the development of endothelial dysfunction for example hypercholesterolemia, hyperhomocysteinemia, diabetes mellitus and smoking. Many investigational and currently used drugs have a beneficial effect on endothelial cells through variable mechanisms, mainly through their antioxidant and antiinflammatory effects. Several drugs which are used for cardiovascular diseases appears to have a protective effect on endothelial cells. The main focus of this review will be on endotheliumderived vasoactive substances, risk factors and some pharmacological substances that can improve endothelial function.