A review. Therapeutic agents affecting specific targets in cancer cells have begun to occupy an important position in cancer treatment. These treatments, known as targeted therapies, exert their effect via two main mechanisms. One group of these therapeutic agents is monoclonal antibodies which block receptors on the cell surface, deliver antineoplastic agents or facilitate the immune response. A second group of agents are small mols. which enter the cell and interrupt signaling pathways necessary for cancerous growth. Several drugs which affect single targets are used successfully for malignancies outside the brain in oncol. practice. Imatinib mesylate, gefitinib, erlotinib, bevacizumab, inhibitors of farnesyltransferase and multitargeted agents such as antineoplastons (ANP) are also being used in extensive clin. studies in neuro-oncol. Imatinib, gefitinib and erlotinib do not appear to have antitumor activity in high-grade gliomas as single agents, but may produce a synergistic effect with chemotherapy. ANP shows promising results in phase II studies of high and low grade gliomas, brain stem gliomas and a number of responses in preliminary reports in primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumors and multicentric gliomas. The efficacy of these agents has not yet been confirmed in phase III studies. This chapter reviews the most important mol. targets, mechanisms of action and results of clin. trials of new generation of antineoplastic drugs that selectively destroy neoplastic cells in brain tumors.