Multivariate analyses have consistently identified a number of patient, tumor, and treatment variables that are significant prognostic factors for overall survival in patients with high-grade glioma. Age, performance status, mental status, tumor grade and histology, and extent of surgical resection are among the most significant prognostic factors influencing survival. Recently, we showed that normal versus abnormal baseline Folstein mini-mental status examination score is a significant prognostic factor in younger patients (age </=42), suggesting that mental status may be a more important determinant of clinical outcome than physical functioning in patients with high-grade glioma. Among tumor variables, tumor grade and histology appear to have the greatest effect on survival. A recursive partitioning analysis of three Radiation Therapy Oncology Group trials showed that among patients under 50 years of age, astrocytoma with anaplastic or atypical foci was associated with significantly improved survival compared with glioblastoma. An oligodendroglial component was also associated with improved survival in patients with grade 3 astrocytoma. In addition, combined loss of chromosome arms 1p and 19q is associated with improved chemosensitivity and overall survival in patients with pure oligodendroglioma. Among the treatment variables tested, extent of resection appears to be the most consistent prognostic factor. Gross total resection is associated with significantly improved survival compared with biopsy only. These models are capable of grouping patients into distinct prognostic subgroups with median survivals ranging from less than 5 to more than 50 months and thus provide useful information for future clinical trial design.