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The past decade has brought about major changes in the way we classify and have begun to approach patients with high-grade glioma. As we trend toward personalized medicine, we are now able to utilize the molecular characteristics of each individual's tumor in order to tailor their treatment, particularly if the patient is elderly or has a poor performance status at baseline. We address the state of the practice as of 2016 in regard to chemotherapy, immunotherapy, and tumor-treating fields. The goal of this review is to enhance readers’ understanding of the nuances that are allowing clinicians to tailor the treatment of high-grade glioma more specifically.