The median overall survival and, more importantly, the 2-year survival rate of patients with newly diagnosed glioblastoma are increased by the administration of combined temozolomide and radiotherapy, which has recently become the new standard of treatment in patients with a histological confirmation of diagnosis. Moreover, the assessment of O(6)-methylguanine-DNA methyltransferase gene promoter methylation has clarified the impact of this approach, and improved upon the interpretation of doubtful cases after concurrent radiotherapy/temozolomide treatment. Therefore, future strategies in the treatment of glioblastoma patients will include stratification for MGMT methylation status, and various approaches based on epigenetic features are currently under investigation.