Gliomas are considered as locally aggressive diseases, consequently, surgery and radiotherapy are the basic therapies of the glial tumors. Nevertheless, the long-term ineffectiveness of the local treatment modalities and the frequently observed relapses explain the unmet medical need for the elaboration of effective systemic treatment regimes. In the last few decades of the 20th century, the use of different chemotherapeutic agents and their combinations, and the alternative administration of drugs have been in the therapeutic forefront of gliomas, whereas, later, in the first years of this century temozolomide was introduced to the everyday clinical practice as the most effective "anti-glioma" medicine, and it is still widely used both in monotherapy and in different combinations. Nevertheless, in the last two decades, considering the recognition of different predictive molecular markers, different targeted therapies, e.g. VEGFR inhibitor agents were also introduced into the routine clinical practice, and there have been promising results published in immunotherapy trials in the recent years, as well. Besides the promising results with the novel systemic therapies, it should be emphasized that both in the primary and the salvage care of the glial tumors the most effective treatment options are the individualized combinations of local and systemic treatment modalities, with the proper interpretation of brain imaging data and patient-centered clinical management.