Angiogenesis is an important natural process occurring in the body, both in health and in infirmity, that is controlled by angiogenesis-stimulating growth factors and angiogenesis inhibitors. Uncontrolled angiogenesis in a tumor can result in both tumor growth and metastasis. Vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) are major players in many human malignancies and contribute directly to disease outcome. There is compelling evidence indicating that the beneficial effects of VEGF and VEGFR can be targeted as antiangiogenic therapy. Many of the agents have shown promising results in cell culture preclinical and animal models. Some of these agents have been tested in clinical trials as well. This review discusses the clinical significance of VEGF/VEGFR in human cancer, summarizes the more recent progress in the field, and further emphasizes the current development of agents that block VEGFR/VEGFR as angiogenesis inhibitors and the therapeutic significance of these agents in clinical trials.