Immunotherapies continue to hold promise for the treatment of glioblastoma, a malignant central nervous system tumor. Thus far, success utilizing this approach has been limited. Negative trials with vaccines and immune checkpoint inhibitors have been unable to demonstrate improvement in survival, however, they have provided insights into hurdles which need to be overcome. Ongoing investigations into modulation of the highly suppressed tumor immune microenvironment, direct simulation of the immune system for proinflammatory effect, and the use of cellular therapies will help inform future therapeutic directions.