Primary central nervous system tumors are infrequent lesions observed in both pediatric and adult patients that account for a disproportionate amount of cancer related morbidity and mortality. A significant number of advances in neurosurgical and radiation therapy techniques have occurred over the last few decades and yet only small improvements in long-term outcome have resulted. The major reason for this is the ability of these advances to minimize surgical or radiation morbidity on surrounding normal tissue rather than eradicating the microscopic infiltrating disease that remains after up-front standard therapy. As such, a great deal of effort has gone into adjuvant chemotherapy that might complement the standard surgical and radiation approaches. This paper will review the literature on anti-angiogenic therapies in central nervous system (CNS) tumor models and clinical disease, with a focus on anti-angiogenic chemotherapy (also referred to as metronomic or low-dose chemotherapy) and the utilization of this approach in conjunction with standard radiation and surgery. A number of excellent reviews covering related aspects of this topic are also available (1-13).