Interferon-gamma (IFNgamma) is a cytokine that acts on cell-surface receptors, activating transcription of genes that offer treatment potential by increasing tumor immunogenicity, disrupting proliferative mechanisms, and inhibiting tumor angiogenesis. However, abnormally low levels of IFNgamma are produced by tumor cells and local T cells in the glioma microenvironment. Current investigations into the immunomodulating effects of IFNgamma suggest that IFNgamma has the potential to be used clinically in the treatment of brain tumors and as a promising adjunct to other immunotherapeutic modalities. Here the authors review the published literature that highlights the potential role of IFNgamma in the treatment and immunotherapy of malignant gliomas.