The vascular endothelium is a complex modulator of a variety of biological systems and may well be the key to definitive success in the treatment of cardiovascular disorders. Surgically-induced endothelial injury may occur preoperatively during cardiac catheterization and intraoperatively from mechanical manipulation, ischemia, hypothermia, and exposure to cardioplegic solutions. The normal endothelium is antithrombogenic and yet promotes platelet aggregation and coagulation if injured. Vasospasm, occlusive intimal hyperplasia, and accelerated arteriosclerosis can also all occur as a result of endothelial injury. Furthermore, endothelial injury is harmful even in the absence of disruption of its monolayer integrity. Thus, preservation of the endothelium should be an additional objective for all cardiovascular surgeons. Synthetic vascular grafts, cardiac valves, and artificial ventricles do not spontaneously endothelialize and thus usually require some form of anticoagulation to maintain patency. Hence, endothelialization of prosthetic implants became an attractive concept. A number of different methods of obtaining an endothelial lining of prosthetic material has since been developed; these include facilitated endothelial cell migration, and endothelial cell seeding by using either venous or microvascular endothelial cells. Manipulating the endothelium might well provide the next major advancement for therapeutic and preventive measures for cardiovascular disease.