The pulsatile nature of blood flow is a key stimulus for the modulation of vascular cell differentiation. Within the vascular media, physiologic stress is manifested as cyclic strain, while in the lumen, cells are subjected to shear stress. These two respective biomechanical forces influence the phenotype and degree of differentiation or proliferation of smooth muscle cells and endothelial cells within the human vasculature. Elucidation of the effect of these mechanical forces on cellular differentiation has led to a surge of research into this area because of the implications for both the treatment of atherosclerotic disease and the future of vascular tissue engineering. The use of mechanical force to directly control vascular cell differentiation may be utilized as an invaluable engineering tool in the future. However, an understanding of the role of hemodynamics in vascular cell differentiation and proliferation is critical before application can be realized. Thus, this review will provide a current perspective on the latest research and controversy behind the role of hemodynamic forces for vascular cell differentiation and phenotype modulation. Furthermore, this review will illustrate the application of hemodynamic force for vascular tissue engineering and explicate future directions for research.