The criterion standard chemotherapy for gliomas is temozolomide. Temozolomide is taken orally and has a low frequency of serious adverse events, which enormously facilitates its use around the world. Survival is superior by several weeks in patients treated with temozolomide and radiotherapy compared with patients treated with radiotherapy only.20 Bevacizumab (Avastin) was the first US Food and Drug Administration–approved biological therapy designed to inhibit the formation of new blood vessels in tumors. Bevacizumab is a monoclonal antibody that binds to and inhibits vascular endothelial growth factor.21 The basis for bevacizumab's accelerated approval in 2009 for treating recurrent glioblastoma was uncontrolled phase II trials with a total of 215 patients, a single-arm phase II trial of bevacizumab with irinotecan added at progression, and a randomized phase II trial of the same regimen or first-line treatment with the combination of bevacizumab and irinotecan.22 Despite its promise, bevacizumab has not dramatically improved survival in patients with glioma. However, bevacizumab does improve progression-free survival and eliminates the need for steroids to treat edema. Therefore, bevacizumab offers some therapeutic benefits to patients with glioma and can improve their quality of life.23 Not all gliomas are sensitive to anti–vascular endothelial growth factor therapy.24 In addition, some of the tumors that are initially sensitive to the therapy recur with an aggressive phenotype (Figure 3). In fact, magnetic resonance imaging of patients with glioblastomas treated with bevacizumab showed the development of multifocal recurrence and strongly indicated the presence of an infiltrative/invasive pattern.25 In this regard, Bergers and Hanahan26 recently proposed several hypothetical mechanisms that might underlie the evasive resistance of tumor cells to antiangiogenic therapy. These models include an increased capability of the tumor cells to develop an invasive phenotype without promoting angiogenesis. In fact, there is strong evidence that malignant glioma cells adapt to pathological conditions (such as necrosis) or to therapies that challenge angiogenesis by migrating more aggressively into healthy tissue.27 Collectively, these observations indicate that the clinical success of antiangiogenic therapy might depend on its combination with simultaneous therapy aimed at preventing multifocal recurrence by inhibiting tumor infiltration. Preclinical and clinical data have established the effectiveness of antiangiogenic therapies for human malignant gliomas. However, more studies need to be undertaken, with a special focus on identifying the mechanisms of the resistant phenotype and, ultimately, testing combined therapies.