As the cells forming the luminal vascular surface, endothelium regulates both barrier function, and pro- and anticoagulant reactions. Endothelial cells can do this by controlling the expression of cell surface molecules, such as receptors that regulate the hemostatic balance and those that affect permeability across the endothelial monolayer. This regulation occurs in response to environmental stimuli, such as cytokines, which have a central role in inflammation, or glucose-modified proteins, which accumulate in the vasculature in aging and diabetes and are associated with vascular complications. The endothelial cell emerges as a dynamic regulator maintaining homeostasis in the quiescent state and contributing to the pathogenesis of vascular lesions in the stimulated state.