**Abstract**

Malignant pleural mesothelioma (MPM) is an aggressive malignancy with a poor prognosis, principally caused by a prior asbestos exposure. Up to the present, multimodality protocols including surgery with chemotherapy (CT) and/or radiotherapy (RT) represent the therapeutic gold standard for selected patients (epithelial and early-stage MPM). In this context, the aim of surgery is to accomplish the macroscopic complete resection (MCR). There are two main surgical options to obtain MCR—extrapleural pneumonectomy (EPP) and pleurectomy/decortication (PD). The superiority of one surgical approach over the other is still discussed. To date, the decision to carry out one or the other in a multimodal setting is established on surgeons' preference more than on strong scientific evidence. Due to the high morbidity, both surgical techniques should be achieved in tertiary referral centres. In summary, surgery, CT, and RT have failed as single modality therapies with no effects on patients survival. This aspect may be justified by the lack of randomized trials. Thus, novel therapeutic strategies, such as multimodality treatment and targeted agents, seem to prolong the survival and the quality of life. The aim of this chapter is to provide a complete overview of the current surgical approaches to MPM, discussing within the frameworks of pre-operative diagnostic evaluation and multimodality oncological treatments.

**Keywords:** malignant pleural mesothelioma, extrapleural pneumonectomy, pleurectomy/decortication, multimodality treatment, chemotherapy, radiotherapy, target therapy
