Vascular endothelial cells (ECs) play a central role in the control of blood vessel function and circulatory system homeostasis. It is well known that that EC functions are regulated by chemical mediators, including hormones, cytokines, and neurotransmitters, but it has recently become apparent that EC functions are also controlled by hemodynamic forces such as shear stress and stretch (cyclic strain). ECs recognize shear stress and cyclic strain as mechanical stimuli, and transmit the signal into the interior of the cells, thereby triggering a variety of cellular responses that involve alterations in cell morphology, cell function, and gene expression. Impaired EC responses to shear stress and cyclic strain lead to vascular diseases, including hypertension, thrombosis, and atherosclerosis. A great deal of research has already been conducted on the mechanotransduction of shear stress and cyclic strain, and its molecular mechanisms are gradually coming to be understood. However, much remains unclear, and further studies of mechanotransduction should increase our understanding of the molecular basis of the hemodynamic-force-mediated control of vascular functions.