Vascular endothelium is a monocellular layer positioned between the muscular media, or the adventitia in capillaries, and the circulating blood [1]. While it has long been recognized that this tissue acts as a selective sieve to facilitate bi-directional passage of macromolecules and blood gases between tissues and blood, the strategic importance of the endothelium in regulating vascular homeostasis, as well as its protective role, have been more recently described. The critical location of this tissue allows it to sense changes in hemodynamic forces and blood-borne signals. In turn, these stimuli trigger a response that is mediated by the release of a number of autocrine and paracrine substances. For example, myogenic or adrenergic tone are endothelium-independent, yet vascular homeostasis is controlled by a balanced release of endothelium-derived bioactive factors. The loss of the structural and/or functional integrity of the endothelium (i.e. endothelial dysfunction) disrupts this balance, thereby predisposing the vessel wall to vasoconstriction, leukocyte adhesion, platelet activation, mitogenesis, peroxidation, thrombosis, impaired coagulation, vascular inflammation, and ultimately, atherogenesis [2] (Figure 1). The following paragraphs describe how hemorheology interferes with the production of endothelial autacoids, how the endothelium functions, and how it influences vascular flow and hemorheology.