Standard approaches to therapy for malignant glioma provide modest improvement of progression-free survival and overall survival. Almost all patients experiencing glioblastoma eventually progress, and no cure is currently available. During the last decade, we have witnessed a 30% improvement in 2-year overall survival rates, yet glioblastoma continues to cause approximately 13,000 cancer-related deaths in the United States annually. Thus, novel therapies need to be investigated alongside continued development of currently available radiotherapy and chemotherapy options. Because glioblastoma does not typically metastasize outside the brain, development of unique local therapies that are not available for other cancers is feasible. Experimental agents, like scorpion venom-derived chlorotoxin, have been successfully applied in local therapy for glioblastoma. In addition, multiple new gene therapy approaches are emerging for both local and systemic glioblastoma therapy. Lastly, alternating electric fields are being introduced to cancer therapy. This review will discuss these "nonstandard"--outside the box--modalities for therapy for malignant glioma.