Angiogenesis is required for invasive tumor growth and metastasis and constitutes an important point in the control of cancer progression. Its inhibition may be a valuable approach to cancer therapy. Antiangiogenic agents are designed to attack the tumor vasculature and cut off the tumor's supply of nutrients. Systemic blockade of angiogenesis has been recently approved for the treatment of several types of human cancers. Antiangiogenic therapy presents various advantages as compared to conventional treatment. Vascular endothelial growth factor (VEGF) is considered to be one of the most important regulators of angiogenesis and a key target in anticancer treatment. VEGF binding to its receptor (VEGFR) leads to cell proliferation and new vascular formation by tyrosine kinase (TK) pathway. VEGF/VEGFR pathway is becoming attractive target for anticancer drug design. It is believed to be important in the control of angiogenesis. Antiangiogenic therapy based on inhibition of VEGFR was reported to be powerful clinical strategies. In this review, the authors describe the existing literature regarding VEGFR inhibitors in the last few years. We attempt to cover all essential publications on the medicinal chemistry in terms of chemical structure, pharmacological profile and structure-activity relationships.