Immunotherapy is coming to the fore as a viable anti-cancer treatment modality, even in poorly immunogenic cancers such as glioblastoma (GBM). Accumulating evidence suggests that the central nervous system may not be impervious to tumor-specific immune cells and could be an adequate substrate for immunologic anti-cancer therapies. Recent advances in antigen-specific cancer vaccines and checkpoint blockade in GBM provide promise for future immunotherapy in glioma. As anti-GBM immunotherapeutics enter clinical trials, it is important to understand the interactions, if any, between immune-based treatment modalities and the current standard of care for GBM involving chemoradiation and steroid therapy. Current data suggests that chemoradiation may not preclude the success of immunotherapeutics, as their effects may be synergistic. The future of therapy for GBM lies in the power of combination modalities, involving immunotherapy and the current standard of care.