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Despite aggressive surgery, radiotherapy, and chemotherapy, malignant gliomas remain uniformly fatal. To progress, these tumors stimulate the formation of new blood vessels through processes driven primarily by angiogenesis factors. However, the resulting vessels are structurally and functionally abnormal and contribute to a hostile microenvironment that is highly selective for a more malignant phenotype with increased morbidity and mortality. Emerging preclinical and clinical data indicate that antiangiogenesis therapies are potentially effective regarding glioblastoma, and can transiently normalize tumor vessels. This creates a window of opportunity for optimally combining chemotherapeutics and radiation.