Over the last two decades, after establishing the role of postoperative radiotherapy for malignant gliomas, no definitive improvement in survival rate could be observed, despite advances in established treatment modalities such as radiotherapy and chemotherapy. Progress in exploration of the biology of these tumours allowed for translational research projects and the development of rational new approaches, such as gene therapy and immunotherapy, that could interfere with established treatment regimens or be used independently. Possible strategies include the restoration of defective cancer-inhibitory genes, cell transduction or transfection with antisense DNA corresponding to genes coding for growth factors and their receptors, or with the so-called 'suicide genes'. Several antiangiogenic approaches such as administration of thalidomide, protamine, or monoclonal antibodies against vascular endothelial growth factor have been developed, too. Further treatment possibilities include modulation of drug resistance, e.g. by P-glycoprotein antagonists or 06-alkyl-guanine-DNA-transferase inhibitors, inhibition of matrix metalloproteinases, inhibition of protein kinase C and administration of agents such as phenylbutyrate or valproic acid that showed promising antiproliferative effects in vitro. This review discusses the available laboratory and clinical data as well as recent advances in our knowledge about prognostic and predictive factors and their implications for the design of future clinical trials.