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Background The current standard of care for patients with high-grade gliomas includes surgical resection, chemotherapy, and radiation; but even still most patients experience disease progression and succumb to their illness within a few years of diagnosis. Immunotherapy, which stimulates an anti-tumor immune response, has been revolutionary in the treatment of some hematologic and solid malignancies, generating substantial excitement for its potential for patients with glioblastoma. However, to date, the preclinical success of these approaches against high-grade glioma models has not been replicated in human clinical trials. Moreover, the complex response to these biologically active treatments can complicate management decisions, and the neurosurgical oncology community needs to be actively involved in and up to date on the use of these agents in patients with high-grade glioma. In this review, we discuss the challenges immunotherapy faces for high-grade gliomas, the completed and ongoing clinical trials for the major immunotherapies, and the nuances in management for patients being actively treated with one of these agents. Methods We reviewed the literature to summarize the current immunotherapy strategies for high-grade gliomas. Results Preclinical and clinical trials investigating dendritic cell and peptide vaccines, checkpoint inhibitors, and adoptive T cell therapy are highlighted in this review. Conclusions Although immunotherapy has yet to fully fulfill its promise for patients with glioblastoma and improve patient outcomes, there is still excitement that these approaches will eventually lead to durable anti-tumor responses. As neurosurgeons, an understanding of the complex interactions between the standard of care therapies and the other medications used in the treatment arsenal for patients with high-grade brain tumors is crucial to the management of these patients. [ABSTRACT FROM AUTHOR]