In patients with malignant pleural mesothelioma, radiotherapy is useful in the palliation of symptoms of chest pain and painful masses. Prophylactic chest wall irradiation appears to reduce the incidence of chest wall recurrences at incision sites. An area of active ongoing research is the role of high-dose hemithorax irradiation after extrapleural pneumonectomy for early stage disease. In carefully staged patients, this approach has resulted in a marked reduction in local tumor recurrences, although nearly one half of patients subsequently developed isolated distant metastases. Relevant issues for planning postoperative radiotherapy in such patients are highlighted. These multimodality protocols await evaluation within prospective randomized clinical trials, and effective systemic chemotherapy regimens will also need to be integrated into such approaches.