Combined therapy with temozolomide and radiotherapy is a standard treatment and improves the survival for patients with newly diagnosed glioblastoma. However, the prognosis remains poor, with a median survival time of 12–15 months. Currently, several clinical trials of dose-dense temozolomide regimen or molecular-targeting therapies have been performed to overcome the resistance of glioblastoma. In these therapies, rational prognostic biomarkers have also been investigated to predict their outcome and response to treatment. This advanced understanding of the biological markers can help to develop personalized therapies for glioblastoma patients. Generally, due to a reduced tolerance, elderly patients do not seem to benefit from intensive treatment. This population needs individual treatments depended on their age or performance status. In this article, we review the recent studies that can provide personalized therapy for glioblastoma, based on molecular tumor profiling or patients’ physical status.