Gliomas represent the most common CNS cancers in adults. Prognosis for patients harboring malignant gliomas is particularly dismal and, despite current treatment strategies comprising surgery, radiotherapy and chemotherapy, the median survival time after diagnosis is still in the range of just 12 months. In recent years, there has been an increased effort to identify tumor biomarkers that can be used as diagnostic tools, or markers for predicting therapeutic response and prognosis. Investigation of genetic changes has identified several such markers that have shown some success in predicting the most effective therapy. In recent years, however, it has become apparent that the biology of many cancers of the CNS is determined not only by their genetic profile but also their epigenetic profile. Epigenetic biomarkers show great potential in effectively predicting patient prognosis and response to therapy. The eventual application of epigenetic profiling of tumors may help to indicate the most effective tailored therapy for individual patients.