Malignant pleural mesothelioma (MPM) is a relatively rare multifocal pleural tumor with low metastatic potential. Surgery can be used in MPM for diagnostic and therapeutic purposes. Thoracoscopy is a useful tool to obtain tissue biopsy to establish a definitive diagnosis and to perform talc poudrage of the pleural cavity in order to prevent reaccumulation of fluid. Cytoreductive procedures, such as pleurectomy/ decortication (PD) and extrapleural pneumonectomy (EPP) are also used in multimodal treatment protocols. The available evidence until now suggests that EPP offers better palliation of dyspnea and orthopnea due to a trapped lung and ventilation perfusion mismatch and better adjuvant radiation therapy planning when compared to PD. Better local disease control and obvious survival benefit by using EPP instead of PD are at the moment unproven. However, EPP is connected with high mortality and morbidity rates, especially if performed in centers without expertise with this complex procedure. EPP and thoracoscopic parietal pleurectomy are now tested in two ongoing prospective randomized trials for their efficacy in the treatment of this disease. In the absence of any controlled randomized trial, EPP should be considered as part of the treatment of MPM only within the context of a prospective randomized trial or in special centers with expertise in the procedure and always within a tri-modal or four-modal treatment protocol, including also chemotherapy, radiotherapy, intrapleural immunochemotherapy and laser photodynamic therapy.