One of the most promising pathways for the development of new anti-neoplastic agents is targeting tumor vascular endothelium. There is significant preclinical and clinical evidence indicating that tumor neoangiogenesis is critical in pathogenesis and progression of solid tumors, including breast cancer. Of the numerous known growth factors that have been implicated in tumor angiogenesis, vascular endothelial growth factor (VEGF) is one of the important molecules regulating new blood vessel formations and subsequent invasion and metastases. As a result, agents that inhibit VEGF are of substantial interest for the treatment of advanced diseases. More thorough elucidation of mechanisms behind intrinsic and acquired resistance therefore is imperative disease and to identify patients most likely to benefit from treatment options.