In the last decade the endothelium has been shown to play a major role in regulating membrane permeability, lipid transport, vasomotor tone, coagulation, inflammation, and vascular wall structure. These critical endothelial cell functions are extremely sensitive to injury in the form of hypoxia, exposure to cytokines, endotoxin, cholesterol, nicotine, surgical manipulation, or hemodynamic shear stress. In response to injury endothelial cells become activated, tipping the balance of endothelial-derived factors to disrupt barrier function, and enhance vasoconstriction, coagulation, leukocyte adhesion, and smooth muscle cell proliferation. Although these responses likely exist as protective mechanisms, if the stimuli are severe the responses may become excessive, resulting in damaged tissue, impaired organ function, and an abnormal fibroproliferative response. Recent discoveries in the field of vascular biology have led to an expanded understanding of many of the complications of cardiovascular operations. Because of the wide impact endothelial cell dysfunction has on patients with cardiovascular disease, issues pertaining to endothelial biology are in the forefront of research that will affect the current and future practice of cardiothoracic surgery.