High-grade gliomas, including glioblastoma multiforme, anaplastic astrocytoma, and intrinsic pontine, are very difficult to treat in children. Despite aggressive treatment with multimodal therapy, most children with these diseases do not survive. Data from published series support aggressive surgical resection when clinically feasible. Patients who have had aggressive resections tend to have a longer survival than those who have undergone only biopsies or partial resections. Almost all patients with high-grade gliomas respond to radiation therapy, and it is the current mainstay of adjuvant therapy. Radiation therapy also tends to prolong survival, but it is rarely curative. Although responses to chemotherapy have been demonstrated, there are no compelling data indicating that it prolongs survival for this group of patients. Current and proposed studies are combining radiation therapy and/or chemotherapy with agents that have shown preclinical promise as radiosensitizers, anti-angiogenesis factors, growth factor receptor inhibitors, and free radical inducers. Other biologic therapies, including gene therapy, are also being investigated. Improved survival for these patients will likely require combined therapy that includes novel treatment.