VEGF R1, R2, R3 and Neuropilin-1 and -2 are expressed on vascular endothelial cells where they play critical roles in angiogenesis and vessel branching during embryonic development, the female reproductive cycle, and wound healing. These receptors are required for regulating endothelial cell proliferation, migration, and survival. In disease, they are involved in tumor development and vascular leakage. They mediate the mitogenic, angiogenic, and lymphangiogenic effects of PLGF-1, 2, VEGF-A, -B, -C, and -D. VEGF R1, R2, and R3 are receptor tyrosine kinases (RTKs) that form homo- or hetero-dimers, autophosphorylate, and activate multiple downstream signaling cascades in response to ligand binding. Soluble isoforms of VEGF receptors and Neuropilins circulate and can modulate the bioactivity of VEGF factors.