Multimodality treatment including macroscopic complete resection (MCR) is currently the most effective therapy for patients with malignant pleural mesothelioma (MPM). However, the allocation to one of the possible combinations has to be discussed individually since various factors influence the decision making process. In the past years, relevant new information about the disease and the outcome of different treatment modalities have been generated, which allows a more individual allocation to the best treatment. For many years extrapleural pneumonectomy (EPP)-the most aggressive procedure to achieve a MCR-was the first choice in combination with adjuvant or neo-adjuvant chemotherapy and radiation therapy for all patients except those with minimal disease. However, mortality and morbidity of an EPP and the fact, that even with the most radical procedure only MCR and not a complete resection can be achieved, led to shift towards pleurectomy/decortication in most of the centers. But also today, EPP is still a valuable option in selected cases and the entire treatment concept requires a nuanced view, which will be discussed in this review.