Health-related quality of life (HRQOL) has become an increasingly important endpoint in cancer studies; however, the research into the HRQOL of patients with high-grade glioma (HGG) is sparse compared with that for patients with other neoplasms. Owing to the specific location and poor prognosis, it is more important and difficult to study HRQOL in patients with HGG than in those with other tumors; furthermore, the study of HRQOL in patients with HGG differs from that for patients with other tumors. In this review, we identified and compared the most frequently used instruments to assess HRQOL; analyzed specific facets and determinants of HRQOL (such as sex, tumor location and histological classification, depression, and cognitive function), as well as the association between HRQOL and survival; and appraised the effects of new treatments on HRQOL in patients with HGG from randomized controlled trials. Furthermore, we detected broadly existing problems and many contradictory outcomes and gave some proper interpretation and suggestions regarding them.