Atherosclerotic lesions form preferentially at distinct sites in the arterial tree, especially at or near branch points, bifurcations, and curvatures where there is disturbed or oscillatory blood flow. In contrast, straight regions of the vasculature exhibit uniform laminar shear stress, which is atheroprotective. The ability of laminar flow to exert an anti-inflammatory effect on the endothelial cell lining of the blood vessel is revealed by preventing monocyte adhesion, proliferation, and apoptosis. Changes in endothelial cell gene expression in response to laminar shear stress reflect these changes in cell physiology with the demonstration that physiologic flow inhibits the expression of inflammatory genes. Thus, shear stress is critically important in regulating vascular physiology and pathobiology of the vessel wall via the modulation of endothelial cell gene expression.