Situated at the interface between the blood and the inner wall of the vasculature, the endothelium is currently considered as not only a protective barrier but a central player for cardiovascular homeostasis. Indeed, the endothelium is the source of biologically active mediators with opposite effects, vasoconstrictor and vasodilator substances, growth promoting and inhibiting factors, thrombogenic and thrombolytic agents, oxidative and antioxidative determiners. Urocortin, a 40 amino acid peptide, is identified as a member of the corticotropin-releasing factor family. Urocortin has been demonstrated to show diverse effects on cardiovascular system. It is commonly considered that urocortin is a protective agent on vascular function. This book will focus on recent evidence that reveals the beneficial and detrimental effects of urocortin on endothelium.