Glioblastomas are highly vascular tumors. Recent preclinical and clinical investigations have demonstrated that agents targeting angiogenesis may have efficacy in this type of tumor. Antibodies to vascular endothelial growth factor (VEGF), VEGF receptor tyrosine kinase inhibitors, immunomodulatory agents, and soluble decoy VEGF receptors are being studied in this patient population. Unfortunately, treatment inevitably fails. Further studies are needed to understand mechanisms of tumor resistance and to identify other therapeutic targets that mediate angiogenesis.