Shear stress is the tangential force of the flowing blood on the endothelial surface of the blood vessel. Shear is described mathematically for ideal fluids, and in vitro models have enabled researchers to describe the effects of shear on endothelial cells. High shear stress, as found in laminar flow, promotes endothelial cell survival and quiescence, alignment in the direction of flow, and secretion of substances that promote vasodilation and anticoagulation. Low shear stress, or changing shear stress direction as found in turbulent flow, promotes endothelial proliferation and apoptosis, shape change, and secretion of substances that promote vasoconstriction, coagulation, and platelet aggregation. The precise pathways by which endothelial cells sense shear stress to promote their quiescent or activated pathways are currently unknown. Clinical applications include increasing shear stress via creation of an arteriovenous fistula or vein cuff to promote bypass graft flow and patency. Since an abnormal level of shear stress is implicated in the pathogenesis of atherosclerosis, neointimal hyperplasia, and aneurysmal disease, additional research to understand the effects of shear stress on the blood vessel may provide insight to prevent vascular disease.