For nearly 20 years, interstitial brachytherapy has been used as adjuvant treatment for malignant brain tumors in both prospective clinical trials and as part of standard therapy. Numerous publications analyzing the results of this treatment seem to indicate an improvement in median survival for highly selected patients. Some newly diagnosed glioblastoma multiforme, recurrent malignant glioma, brain metastases and possibly low grade gliomas seem to benefit. While Iodine-125 (I-125) remains the most popular radionuclide for brachytherapy, there is a recent move away from temporary high-activity implants to permanent low-activity implants. This review article will concentrate on the results from the University of California, San Francisco, as well as recent series published since 1990. In spite of the increased availability of radiosurgery, interstitial brachytherapy still has a place in the management of these difficult tumors. Semin. Surg. Oncol. 14:79–87, 1998. © 1998 Wiley-Liss, Inc.