High-grade glioma is the most common primary brain tumor, with glioblastoma multiforme (GBM) accounting for 52% of all brain tumors. The current standard of care (SOC) of GBM involves surgery followed by adjuvant fractionated radiotherapy and chemotherapy. However, little progress has been made in extending overall survival, progression-free survival, and quality of life. Attempts to characterize and customize treatment of GBM have led to mitigating the deleterious effects of radiotherapy using hypofractionated radiotherapy, as well as various immunotherapies as a promising strategy for the incurable disease. A combination of radiotherapy and immunotherapy may prove to be even more effective than either alone, and preclinical evidence suggests that hypofractionated radiotherapy can actually prime the immune system to make immunotherapy more effective. This review addresses the complications of the current radiotherapy regimen, various methods of immunotherapy, and preclinical and clinical data from combined radioimmunotherapy trials.