Objective: To summary the recent advances in molecular research of glioblastoma (GBM) and current trends in personalized therapy of this disease. Data Sources: Data cited in this review were obtained mainly from PubMed in English up to 2015, with keywords "molecular", "genetics", "GBM", "isocitrate dehydrogenase", "telomerase reverse transcriptase", "epidermal growth factor receptor", "PTPRZ1-MET", and "clinical treatment". Study Selection: Articles regarding the morphological pathology of GBM, the epidemiology of GBM, genetic alteration of GBM, and the development of treatment for GBM patients were identified, retrieved, and reviewed. Results: There is a large amount of data supporting the view that these recurrent genetic aberrations occur in a specific context of cellular origin, co-oncogenic hits and are present in distinct patient populations. Primary and secondary GBMs are distinct disease entities that affect different age groups of patients and develop through distinct genetic aberrations. These differences are important, especially because they may affect sensitivity to radio- and chemo-therapy and should thus be considered in the identification of targets for novel therapeutic approaches. Conclusion: This review highlights the molecular and genetic alterations of GBM, indicating that they are of potential value in the diagnosis and treatment for patients with GBM.