Vascular endothelial growth factor receptor-2 (VEGF R2), also known as kinase insert domain receptor (KDR), is a member of the class III subfamily of receptor tyrosine kinases (RTKs). VEGF R2 is more widely distributed and expressed in all vessel-derived endothelial cells in comparison to VEGF R1. VEGF R2 binds VEGF-A (VEGF121, VEGF165, VEGF189 and VEGF206 splice variants), VEGF-C and VEGF-D. Soluble forms of VEGF R1 and VEGF R2 differ significantly from one another in terms of their abilities to block VEGF-induced cell proliferation and migration. Soluble VEGF R2 cannot compete with VEGF for binding to human endothelial cells expressing both VEGF R1 and VEGF R2, in contrast to soluble VEGF R1. Soluble VEGF R2 can only partially inhibit cell migration, whereas soluble VEGF R1 can almost completely block VEGF-induced cell proliferation and migration. The binding of VEGF to soluble VEGF R2, but not VEGF R1, is also dependent on heparin. The VEGF/VEGF R2 signaling pathway plays an important role in tumor angiogenesis and other diseases where “pathological angiogenesis” is involved. Inactivation of functional VEGF R2 by a blocking antibody can disrupt angiogenesis and prevent tumor cell invasion.