The vascular endothelium is a dynamic structure which lines the entire circulatory and lymphatic systems and interacts with local and systemic stimuli. It plays an important role in such processes as vasoconstriction/vasorelaxation, inflammation, cell proliferation, and hemostasis. Dysfunction of endothelial cells contributes to the development of different diseases including hypertension, atherosclerosis, and peripheral arterial disease, which are commonly seen in patients with chronic diabetes. Various risk factors including low density lipoprotein oxidation, inflammation, thrombosis as well as imbalance between NO and endothelin production are considered to induce the VE dysfunction and associated cardiovascular diseases. Although several interventions such as thrombolytic agents, anti-inflammatory agents, antioxidants, NO donors, endothelin inhibitors and stem cell therapy are used for the treatment of hypertension, atherosclerosis and peripheral artery disease, none of these have been found to exert satisfactory beneficial effects. Thus a great deal of research work needs to be carried out to define the exact molecular targets and develop newer therapies for the treatment of hypertension, atherosclerosis and peripheral vascular disease.