Three to four thousand cases of malignant pleural mesothelioma will occur in the United States this year. Single-modality therapy with radiation plays a role for palliation. Radiation can prevent tumor recurrence at drain/instrumentation sites and provide symptomatic relief of pain and other complaints. Combinations of surgery and radiation also have been attempted with curative intent. The best local control has been found--EPP followed by radiotherapy. Locoregional tumor recurrence can be dramatically reduced with combinations of extrapleural pneumonectomy and radiation therapy. Survival in aggressively treated early-stage patients is excellent. However, the preponderance of death from distant metastases makes the development of better systemic therapy essential. Better therapy also must be developed for patients who are not candidates for extrapleural pneumonectomy.