Glioblastoma (GBM) is the most common primary malignant brain cancer with a dismal prognosis in spite of aggressive treatment options. Although once thought to be an "immune-privileged" site, recent advances have begun to highlight the complex interaction between the immune system and the central nervous system. Thus, great interest has emerged in the ability of immunotherapy to potentially prolong the survival of patients suffering from GBM. Indeed, numerous clinical trials have demonstrated durable responses in late stage disease, as well as, among patients with brain metastasis. A variety of approaches to modulating the immune system exist and their efficacy are currently being investigated in various clinical trials. Here we provide a brief overview of neuroimmunology and explore the various approaches towards priming the immune system against GBM.