With only about 1,500 new cases a year of pediatric brain tumors, as many cases as possible must be enrolled in ongoing multicenter trials if therapeutic advances are to continue. To date, such trials have identified chemotherapeutic agents active against medulloblastoma, demonstrated the benefits of surgical debulking or resection in patients with astrocytic tumors, and shown the usefulness of chemotherapy to delay radiotherapy in very young children with malignant brain tumors. New trials are exploring the uses of intrathecal administration of 4-hydroperoxycyclophosphamide and radiolabeled monoclonal antibodies in brain tumor patients with subarachnoid metastases. The authors describe the results of completed trials of these new therapies, give details on new regimens being tested in ongoing investigations at centers across the nation, and urge the continued referral of children with brain tumors to academic institutions.