The role of surgery in the management of malignant pleural mesothelioma remains controversial. Surgical resection consists of different procedures for diagnostic or therapeutic reasons. The latter includes either an extrapleural pleuropneumonectomy (EPP) or lung-sparing operations like debulking of the parietal and visceral pleura by pleurectomy/decortication (P/D) or extended pleurectomy/decortication, in which further debulking of the diaphragm or pericardium is included. Because of the modest outcome of surgery as single-modality therapy, combinations of chemotherapy, surgery, and radiation therapy were initiated as a new treatment strategy to improve prognosis. The observations that patients treated with P/D had an equal to better outcome than those treated with EPP, and that EPP with perioperative chemotherapy was better than EPP alone, raises the issue whether performing a P/D with perioperative chemotherapy would result in a further improvement of outcome with a lower operative mortality than with EPP and perioperative chemotherapy. This is the rationale for the next European Organisation for Research and Treatment of Cancer trial exploring the feasibility of P/D with perioperative chemotherapy.