BACKGROUND: Diffuse malignant pleural mesotheliomas (DMPMs) are highly lethal tumors that are becoming more common. Standard management approaches have provided limited effectiveness. METHODS: The literature on management has been revised, and the authors present their data on outcomes for 120 patients treated with an aggressive trimodality approach. RESULTS: An aggressive trimodality approach including extrapleural pneumonectomy followed by chemoradiation produces low mortality and acceptable morbidity. The five-year survival rate in patients with epithelial histology and negative nodes approaches 40%. CONCLUSIONS: Nodal status and histologic subtype are major predictors for survival in patients with early DMPM. A uniformly accepted staging system would allow comparison of treatment approaches from various institutions. More effective management interventions are required.