The treatment of malignant glioma remains problematic. Surgical removal followed by external beam irradiation represents a standard treatment that has demonstrated a prolonged time to progression and survival. However, the capacity to locally invade normal brain invariably leads to formation of a recurrent tumor most often immediately adjacent to the site of resection. This clinical everyday experience prompts the hypothesis that improved local control of the tumor may translate into a delayed time to progression and possibly survival, specifically because systemic chemotherapy for most of these tumors has failed to significantly improve survival. Local treatment strategies including chemotherapy, gene therapy, and immunotherapy are rapidly developing and progressing to clinical trials. Several theoretical considerations suggest that these approaches may be promising in the treatment of brain tumors.