Cancer represents perhaps the most formidable challenge in medicine and science in general. Currently, gliomas are one of the most deadly cancers. Despite aggressive therapy using surgery, radiotherapy and chemotherapy, the prognosis of glioma patients is very poor. The design of new therapies for these tumors is therefore mandatory. Molecular medicine is based on the discovery of fundamental molecular components that determine normal cellular behavior, and are aberrant in cancer cells, and in the subsequent exploitation of these new uncovered targets to generate specific and nontoxic treatments for cancer. In addition with the activation or amplification of oncogenes, progressive inactivation of tumor suppressor genes is one of the characteristics of the malignant progression of gliomas. One of the most promising approaches of gene therapy is the transfer of such tumor suppressor genes to cancer cells. In gliomas, p53, p16 and Rb abnormalities are present in the vast majority of gliomas. Restoration of the wild-type functions of these genes results in either apoptosis or suppression of glioma growth with very low toxicity. This review highlights a small sample of areas where conceptual and practical advances in molecular biology are changing our understanding of the pathogenesis of these tumors.