Multidisciplinary treatment strategies for patients with malignant brain tumors have resulted in only small gains in terms of prognosis in spite of the use of aggressive therapy. There is a growing realization that a paradigm shift is needed in the conceptual approaches to glioma therapy. Such approaches will rely on identification and modification of key cellular targets that define the biological behavior of these tumors. Among the targets for such treatment approaches, tumor angiogenesis has captured the attention of not only the medical field but also of the lay public because of its conceptual departure from traditional methods of cancer therapy. Angiogenesis and vascular proliferation are particularly important in the growth and progression of malignant gliomas and are used as indicators of the degree of malignancy. Recent studies have helped us gain a better understanding of the molecular mediators of this process. It is now evident that after the initial formation of malignancy the continued growth of a glioma is critically dependent on its angiogenic potential. Hence, several approaches to control angiogenesis are being developed and tested. Preliminary results from clinical studies have shown that angiogenesis inhibition is a valid approach as a therapeutic strategy against gliomas but it is also becoming evident that inhibition of individual modulators of this process may not yield the expected impact on prognosis. To fully realize the potential of antiangiogenic therapy, a deeper understanding of the interplay between the tumor vasculature and its environment is needed. Angiogenesis inhibitors have made the transition from preclinical studies to the clinical arena; it remains for ongoing human trials of such agents to fully explore the feasibility and efficacy of these agents in order to exploit the potential of this approach.