The endothelium is critically involved in the regulation of vascular function through its barrier role, via interaction with circulating cells such as platelets, which then release vasoactive or growth regulating agents, through production of substances which may modulate vascular tone and smooth muscle cell growth and also exert antithrombotic effects. The release of serotonin, adenosine diphosphate (ADP), or growth factors from platelets adhering to damaged endothelium, the release of endothelium-derived relaxing or contracting factors (nitric oxide, prostanoids, endothelin), the production of growth factors, all of which exert their effects in paracrine or even autocrine fashion, are some of the mechanisms whereby the endothelium influences vascular tone and growth and platelet aggregation. In different conditions such as hypertension, atherosclerosis, diabetes, heart failure, ischemic heart disease, sepsis, and shock, dysfunction of the endothelium plays an important pathophysiological role through reduction or enhancement of the release of these different products with significant hemodynamic and trophic effects. Therapeutic interventions targeting the endothelium hold promise in the treatment and prevention of some cardiovascular diseases and their complications.