Advances in medical and surgical treatments in the last few decades have resulted in quantum leaps in the overall survival of patients with malignant disease outside the central nervous system, whereas survival of patients with malignant gliomas (World Health Organization Grades III and IV) has remained essentially unchanged. Resection and external-beam fractionated radiotherapy remain the pillars of therapy for malignant gliomas and have shown significant beneficial effects on outcome in many clinical studies. On the other hand, numerous human trials with adjuvant agents, most of them administered systemically and causing serious complications and side effects, have not succeeded in achieving a noteworthy additional extension of survival duration, or have done so only with a considerable deterioration in the quality of life of the treated patients. The concept of local invasiveness of gliomas is not new, but only in the last one to two decades has significant attention been focused on the cell biology and molecular genetics of gliomas. Improved understanding of the fundamental features of tumor cells has resulted in the introduction and increasing clinical use of local therapies in which practitioners opt for spatially defined delivery methods and tumor-selective agents specifically designed to be used in the environment of a brain invaded by glioma. In this review, the authors summarize the key findings in some of the most important clinical studies of locally administered treatments for malignant glioma. A few such therapies have emerged in the last decade, and have shown considerable antitumor activity and a favorable profile of local and systemic side effects. These include biodegradable polymers for interstitial chemotherapy, targeted toxins administered by convection-enhanced delivery, and intra- and peritumorally injected genetically modified viruses conferring glioma-selective toxicity. In addition, areas of possible improvement of these therapies and essential further developments are outlined.