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The frictional forces associated with blood flow expose vascular endothelium in arteries to a complex and highly dynamic shear stress distribution. The ability of endothelial cells to respond to shear stress is essential for arterial vasoregulation in response to acute hemodynamic changes and for vascular wall remodeling following chronic changes in blood flow. Furthermore, endothelial responsiveness to shear stress may play a role in the localization of early atherosclerotic lesions. Shear stress elicits a wide range of humoral, metabolic, and structural responses in endothelial cells. These include activation of ion channels and of G proteins, induction of oscillations in intracellular calcium concentration, alterations in the expression of various important genes, and extensive cytoskeletal reorganization. Mechanisms of shear stress sensing and transmission in endothelium are discussed in light of the complex shear …