Traditionally, cytotoxic drugs have played a limited role in the treatment of brain tumors, but important advances in chemotherapy have occurred during the past decade. Certain central nervous system (CNS) malignancies are remarkably chemosensitive. These include primary CNS lymphoma, medulloblastoma, oligodendroglioma, and intracranial germ-cell tumors. This review focuses on advances in the chemotherapy of these chemosensitive tumors and also discusses the potential use of chemotherapeutic agents, both cytotoxic and cytostatic, in other brain tumors, such as glioblastomas and anaplastic astrocytomas. In addition, a brief description of future directions that may hold promise, including high-dose chemotherapy with stem-cell rescue, blood-brain barrier disruption, and regional treatment using controlled-release biodegradable polymers, is included.