Endothelial cells (EC) exhibit a wide range of functionally distinct subphenotypes including: arterial, venous, as well as the lesser understood “tip”, “stalk”, and “phalanx” EC. The arterial-specific phalanx EC are perhaps most desirable as delivery vehicles for lining the lumens of small diameter vascular grafts in order to minimize thrombosis/arteriosclerosis while the proangiogenic tip/stalk EC would generate the most robust cells for ischemic transplantation and for screening antiangiogenic compounds. This project focused on the in vitro derivation of these distinct subpopulations of EC so that they can be tailored, as needed, for studying disease or repair. From these studies, human ESC and iPS cells have been successfully derived into endothelial cells. Data indicates that tip/stalk and phalanx endothelial cells can be generated and isolated from human ESC. Moreover, the mechanical signal from shear stress does aid in differentiation of endothlelial cells from vascular progenitor cells. However, stability of these subphenotypes has not yet been established.