The endothelium is a thin mono-cellular layer which covers the inner surface of the blood vessels, separating the circulating blood from the tissues and also has the responsibility for uninterrupted maintenance of circulation to all the vital tissues. Endothelium is a very active organ, it works as a receptor-effector organ and responds to each physical or chemical stimulus with the release of the appropriate substance with which it may maintain vasomotor balance and vascular-tissue homeostasis. It has the property of producing, independently, both agonistic and antagonistic substances that help to keep homeostasis and its function is not only autocrine, but also paracrine and endocrine. In this way it modulates the vascular smooth muscle cells producing relaxation or contraction, and therefore vasodilatation or vasoconstriction. The vascular endothelium is vulnerable to maximum wear and tear due to its positioning and requires prompt regeneration of the cells. Whenever the imbalance between substances with vasodilating, antimitogenic, and antithrombogenic properties and substances with vasoconstricting, prothrombotic and proliferative characteristics takes place, it causes a pathological condition known as endothelial dysfunction. These substances intervenes in cell proliferation and migration, in leukocyte adhesion and activation and in immunological and inflammatory processes, further which is responsible for apoptosis of vascular endothelial cells resulting in overall endothelial dysfunction and vasculopathy. This book discusses, in further detail, the risk factors, and the role of endothelial dysfunction in cardiovascular diseases and therapeutic approaches to dealing with endothelial dysfunction.