Malignant mesothelioma originates from the mesothelial cells of the pleural and peritoneal cavities as well as the pericardium and tunica vaginalis, which is a devastating neoplasm with a strong etiological relationship with asbestos exposure. The incidence is rising worldwide, with the peak incidence in most industrialized counties expected to occur in the year 2020. Given the disappointing results of the single standard therapeutic modality, the combination of extrapleural pneumonectomy, chemotherapy, and radiotherapy has been attempted in order to reduce local recurrence and distal spread. Combined modalities have a better prognosis in selected patients with epithelioid histology, clear resection margins, and no positive extrapleural nodes. Chemotherapy using new antimetabolite agents in combination with platinum compounds is useful for palliation and can improve both survival and quality of life compared with single-agent cisplatin.