Health-related quality of life (HRQOL) has become an important outcome measure in clinical trials in primary brain tumor (i.e., glioma) patients, because they have an incurable disease. HRQOL is assessed using self-reported, validated questionnaires, addressing physical, psychological, emotional, and social issues. In addition to generic HRQOL instruments, disease-specific questionnaires have been developed, including for brain tumor patients. For the analysis and interpretation of HRQOL measurements, low compliance and missing data are methodological challenges. HRQOL in glioma patients may be negatively affected by the disease itself as well as by side effects of treatment. But treatment with surgery, radiotherapy, and chemotherapy may improve patient functioning and HRQOL, in addition to extending survival. Although HRQOL has prognostic significance in brain tumor patients, it is not superior to well-known clinical parameters, such as age and performance status. In clinical practice, assessing HRQOL may be helpful in the communication between doctor and patient and may facilitate treatment decisions.