Angiogenesis, the recruitment of new blood vessels is a crucial mechanism required for both tumor growth and metastasis. Advances in the understanding of the molecular mechanisms underlying the angiogenesis process have led to the discovery of a variety of pharmaceutical agents with antiangiogenic activity. The potential application of these angiogenesis inhibitors is currently under intense clinical investigation. Decades of investigation suggest that vascular endothelial growth factor (VEGF) and its receptors, particularly VEGF receptor 2 (VEGFR2, or kinase insert domain-containing receptor, KDR), play a critical role in tumor-associated angiogenesis. KDR, therefore, represents a good target for therapeutic intervention. A number of agents designed selectively for targeting KDR are being evaluated in various phases of clinical trials in cancer patients. This manuscript reviews briefly the biology of VEGF family of ligands and receptors and of KDR in particular. The attempts to develop effective KDR antagonists, including small molecules, antibodies and others, for therapeutic purposes are discussed comprehensively with special emphasis on tumor angiogenesis.