Glioblastoma multiforme (GBM) is a highly malignant primary brain cancer with a dreadful overall survival and for which treatment options are limited. Recent breakthroughs in novel immune-related treatment strategies for cancer have spurred interests in usurping the power of the patient's immune system to recognize and eliminate GBM. Here, we discuss the unique properties of GBM's tumor microenvironment, the effects of GBM standard on care therapy on tumor-associated immune cells, and review several approaches aimed at therapeutically targeting the immune system for GBM treatment. We believe that a comprehensive understanding of the intricate micro-environmental landscape of GBM will abound into the development of novel immunotherapy strategies for GBM patients.