Glioblastoma multiforme (GBM) is the most common and lethal malignant primary brain tumor. It is classified by the World Health Organization (WHO) in the group of diffusely infiltrating astrocytomas, representing up to 50% of all primary brain gliomas, and carries the poorest prognosis. Aberrant genetic events and signaling pathways have clearly demonstrated that GBM is highly anaplastic and a morphologically highly heterogeneous tumor. Understanding the genetic alterations, specific molecular biomarkers and proliferative pathways may promote therapeutic development for the management of GBM. Age, Karnofsky performance score, histology, position and the extent of tumor resection have been identified as potential prognostic factors for patients with GBM. In this study, we review the molecular characterization of tumor cells, the current standard of care for patients diagnosed with GBM, including gross or near-total resection of the tumor, followed by radiotherapy, stereotactic brachytherapy, chemotherapy and new targeted therapies. Thus, we conclude that multimodal approaches for the treatment of patients with GBM may significantly improve their prognoses.