The most common primary brain neoplasm is glioblastoma multiforme, which is associated with a dismal prognosis. Despite the recommended treatment regimen of aggressive surgical resection, radiation, and chemotherapy, the median survival remains approximately only 14 months. Due to these minimal improvements in survival of patients despite recent advances in conventional treatments, new modalities such as immunotherapy are being investigated and studied. A hurdle to developing effective immunotherapy is the immunosuppressive characteristics that are the hallmark of malignant gliomas. Effective therapeutic strategies will require overcoming these mechanisms, by augmenting tumor antigen presentation, perhaps in a setting isolated from the tumor microenvironment. The heterogeneity of potential glioma antigens warrants potential targeting of multiple tumor-specific antigens, and discovery and investigation of additional antigens. This article describes the current strategies and principles of immunotherapy for malignant gliomas.