Glioblastoma (GBM) is the most aggressive glial tumor of the central nervous system. Despite intense scientific efforts, patients diagnosed with GBM and treated with the current standard of care have a median survival of only 15 months. Patients are initially treated by a neurosurgeon with the goal of maximal safe resection of the tumor. Obtaining tissue samples during surgery is indispensable for the diagnosis of GBM. Technological improvements, such as navigation systems and intraoperative monitoring, significantly advanced the possibility of safe gross tumor resection. Usually within six weeks after the surgery, concomitant radiotherapy and chemotherapy with temozolomide are initiated. However, current radiotherapy regimens are based on population-level studies and could also be improved. Implementing artificial intelligence in radiotherapy planning might be used to individualize treatment plans. Furthermore, detailed genetic and molecular markers of the tumor could provide patient-tailored immunochemotherapy. In this article, we review current standard of care and possibilities of personalizing these treatments. Additionally, we discuss novel individualized therapeutic options with encouraging results. Due to inherent heterogeneity of GBM, applying patient-tailored treatment could significantly prolong survival of these patients.