Trimodality treatment of malignant pleural mesothelioma with cytoreductive surgery followed by radiation and chemotherapy has resulted in long-term survival for a select group of patients. Knowledge of the similarities and differences between the two operations that have evolved-extrapleural pneumonectomy and pleurectomy/decortication-is prerequisite to understanding the complex issues associated with patient selection, diagnosis, pathologic staging, preoperative assessment, perioperative management, and adjuvant treatment. Both operations are technically complex and should only be performed at experienced high-volume centers.