Vascular endothelial growth factor and its receptor (VEGF-VEGFR) system play a critical role in the regulation of angiogenesis and lymphangiogenesis in vertebrates. Each of the VEGFs has specific receptors, which it activates by binding to the extracellular domain of the receptors, and thus regulates the angiogenic balance in the early embryonic and adult stages. However, de-regulation of the VEGF-VEGFR system is directly implicated in various diseases, particularly cancer. Moreover, tumor growth needs a dedicated blood supply to provide oxygen and other essential nutrients, and tumor metastasis requires blood vessels to carry tumors to distant sites, where they can implant and begin the growth of a secondary tumors. Thus, investigation of signaling systems related to the human disease, such as VEGF-VEGFR, will facilitate development of treatments for such diseases.