Atherosclerosis develops primarily at arterial bifurcations or curvatures, where flow is oscillatory, whereas vascular segments exposed to shear stress are protected. We showed that local, endothelial-specific angiotensin type 1 receptor (AT1R) expression may be pathologically significant: 1) endothelial expression of AT1Rs, which transduce most known effects of AngII, localizes to low flow, plaque-prone sites in the aorta, and 2) in vitro, endothelial AT1R expression is downregulated by shear stress. Recent data has allowed us to define how shear stress regulates AT1R expression acutely, through interaction with caveolin-1 and internalization. This process is important for shear stress-dependent activation of ERK1/2. We have also found that the hemodynamic environment may influence the expression of other components of the renin-angiotensin system, pointing to a localized tissue regulation of angiotensin II release and activity. Our findings illustrate the many levels at which shear stress orchestrates vascular function.