Endothelial cells form the inner lining of blood vessels. The endothelium displays remarkable heterogeneity in structure and function. Phenotypic diversity reflects the ability of the endothelium to meet the demands of the underlying tissue. In addition to their critical role in homeostasis, endothelial cells are affected by, and contribute to, many pathophysiological states. In allotransplantation, several unique factors influence the status of the endothelium. These include the health of the donor organ, the nature of the preservation protocol, activation of humoral and cell-mediated immune responses, and nonimmune factors such as ischemia-reperfusion and immunosuppressant therapy. The goal of this review is to provide a conceptual framework for approaching the endothelium in allotransplantation.