To date, surgery and irradiation remain the standard therapies for anaplastic astrocytoma (AA, WHO grade III) and glioblastoma multiforme (GBM, WHO grade IV). Due to infiltrative tumor growth a complete surgical resection is never achieved and more than 90% of the tumors will recur within 2 cm of the primary tumor location. Postoperative radiotherapy prolongs survival but is not curative and prognosis remains poor with only a few patients being alive 2 years after diagnosis. Over the past decades multiple trials dealt with the question of whether chemotherapy (CT) may influence the outcome of malignant brain tumor patients. In general, the results have been disappointing with one exception: chemosensitivity and prolonged survival after CT have been demonstrated for tumors of oligodendrogial lineage. Drugs showing some activity in malignant brain tumors and therapeutic concepts will be discussed.