Located between circulating blood and vessel wall, vascular endothelial cells (ECs) are constantly exposed to shear stress resulting from blood flow. The mechanical actions of shear stress can be detected by mechanosensors on ECs and converted into specific signaling pathways to mediate the structural and functional remodeling. Patterns of shear stress may contribute to the focal distribution of atherosclerotic lesions. Here, we review recent advances regarding the roles of shear stress in atherogenesis.