In this article, we explain the current trimodality approach used to treat malignant pleural mesothelioma. Our current approach employs extrapleural pneumonectomy as the cytoreductive procedure followed by combination chemoradiotherapy. Trimodality therapy was performed at the Dana-Farber Cancer Institute/Brigham and Women's Hospital Thoracic Oncology Program. From 1980 to 1995, we prospectively followed up a series of 120 patients with confirmed malignant pleural mesothelioma who underwent trimodality therapy. Two- and 5-year survival rates for the entire cohort were 45% and 22%, respectively. Survival rates were 65% and 27%, respectively, at 2 and 5 years for patients with epithelial histology. Patients with sarcomatous or mixed histology had the poorest prognosis, with 2- and 5-year survival rates of 20% and 0%, respectively. For patients with epithelial tumors and negative nodes, survival at 2 and 5 years was 74% and 39%, respectively. Extrapleural pneumonectomy in the context of trimodality therapy is a potential surgical option for a selected group of patients with malignant pleural mesothelioma.