PURPOSE Gliomatosis cerebri is a rare, diffuse involvement of the central nervous system by a malignant glioma that permeates the brain extensively without destroying the neural architecture and involves more than two lobes. In this study, we sought to assess the role of radiotherapy (RT) and identify prognostic factors in gliomatosis cerebri. METHODS AND MATERIALS Thirty patients who received RT at a single institution and had radiographic follow-up were retrospectively reviewed with respect to outcome, radiation parameters, extent of surgery, and chemotherapy. All cases were analyzed histologically and documented. All pathology slides and radiology images were reviewed. RESULTS The median age at diagnosis was 38.6 years (range 16-68). The median follow-up was 12.8 months (range 3-110). The mean radiation dose was 54.9 Gy, given in a mean of 28 fractions. Radiographic improvement or disease stabilization was achieved in 87% of patients. Clinical improvement was observed in 70%. The median time to progression was 10 months, and it was significantly longer for patients <40 years old (p = 0.0007) and for patients having a tumor histologic subtype other than glioblastoma (p = 0.01). The median overall survival was 18 months and was also longer for patients <40 years (p = 0.0001) and for patients having nonglioblastoma histologic features (p = 0.007). Extensive surgery, administration of chemotherapy, or increased RT volume improved neither overall survival nor the time to disease progression. CONCLUSION RT is effective against gliomatosis cerebri. Patients who are young and have a nonglioblastoma tumor histologic subtype perform more favorably. In this analysis, no role for chemotherapy, extensive surgery, or whole-brain RT was found.