The incidence of malignant pleural mesothelioma in Europe will peak between 2015-2020. Key molecular alterations involve inactivation of tumor suppressors p16 INK4A/p14ARF and NF2. Pemetrexed plus cisplatin is standard first-line chemotherapy. Vinorelbine may be used second-line. Selected patients benefit from multimodality therapy including neoadjuvant chemotherapy, extrapleural pneumonectomy, and potentially radiotherapy, though novel targeted agents have shown limited success so far.