Health-related quality of life is increasingly becoming an important end point in cancer research. Until recently, relatively little was known about the health-related quality of life of glioblastoma multiforme patients. This is due to the relative scarcity of this disease compared with other cancers and its dismal prognosis. Now, there is progress in the treatment of this tumor: new (combination) treatments will be studied in randomized trials and health-related quality will be incorporated as a (secondary) end point next to progression-free survival. Glioblastoma multiforme patient health-related quality of life may also have prognostic significance and may, therefore, be used with the individual patient to tailor treatment. This review aims to chart the history of glioblastoma multiforme and treatment, reporting on the latest health-related quality of life tools and research findings.