Glioblastomas are among the most vascular tumors because they oversecrete vascular endothelial growth factor (VEGF), a potent stimulator of angiogenesis. Consequently, new drug regimens are being developed to target the VEGF signaling pathway in an attempt to halt tumor growth. Antibodies that bind VEGF, decoy molecules that sequester VEGF, and small molecule tyrosine kinase inhibitors that block receptor activation are being tested. Preliminary results with these agents have been promising, with prolonged progression-free survival reported. The antipermeability effects of anti-VEGF agents have important consequences for tumor imaging and for patient quality of life by decreasing corticosteroid dependence. However, because most patients eventually relapse, more work is needed to understand mechanisms of disease escape, including vascular co-option of native brain blood vessels.