Glioblastoma (GB) is a refractory malignancy with limited treatment option. Despite current standard of care, GB still has a dismal prognosis. Although GBs are highly malignant and incurable, significant advances in the understanding of the molecular pathology of GBs and associated cell signaling pathways have opened opportunities for new therapies for both newly diagnosed and recurrent GB patients. Gene expression profiling is now being incorporated into a new generation of personalized clinical trials. Furthermore, upcoming trials with immune check-point inhibitors as a new clinical trial paradigm and other immunotherapies are potentially becoming newly advanced treatment modalities for patients in the near future.