Angiogenesis is of great importance to a variety of normal physiological processes and pathological disorders. It is tightly regulated by many mechanisms, among which vascular endothelial growth factor (VEGF) is one of the most potent promoters. VEGF binds and activates its specific receptor tyrosine kinases, especially vascular endothelial growth factor receptor-2(VEGFR-2). VEGFR-2 mediates the key functional and biochemical effects of VEGF in endothelial cells including proliferation, migration, survival, and permeability. Following its binding to VEGF, VEGFR-2 dimerizes and undergoes autophosphorylation on tyrosine residues within its cytoplasmic portion. This creates docking sites for adapter molecules to be recruited through their Src homology domain-2 (SH2). These adapter molecules can then initiate the activation of downstream signaling cascades. Further down-stream effector molecules are activated, and regulate the biological effects of endothelial cells. It is also foound that VEGF/VEGFR-2 signaling pathway may negatively regulate the function of human monocyte-derived mature dendritic cells (DCs) as well as the maturation of immature-DCs. Advances in the understanding of the VEGF/VEGFR-2 signaling pathway may contribute to the discovery of kinds of pharmaceutical agents.