Glioblastoma (GBM) is the most common malignant brain tumor. Despite multimodality treatment with surgical resection, radiation therapy, chemotherapy, and tumor treating fields, recurrence is universal, median observed survival is low at 8 months and 5-year overall survival is poor at 7%. Immunotherapy aims to generate a tumor-specific immune response to selectively eliminate tumor cells. In treatment of GBM, immunotherapy approaches including use of checkpoint inhibitors, chimeric antigen receptor (CAR) T-Cell therapy, vaccine-based approaches, viral vector therapies, and cytokine-based treatment has been studied. While there have been no major breakthroughs to date and broad implementation of immunotherapy for GBM remains elusive, multiple studies are underway. In this review, we discuss immunotherapy approaches to GBM with an emphasis on molecularly informed approaches.