Therapeutic options for the treatment of malignant pleural mesothelioma include chemotherapy, radiotherapy, and surgery. The principal surgical options are pleurectomy and decortication or extrapleural pneumonectomy. These cytoreductive procedures are generally used in conjunction with other treatment modalities. Pleurectomy and decortication originally were pursued to achieve pleural apposition, but they have had limited success in eradication of tumor and long-term cure. Novel treatment options include pleurectomy and decortication combined with phototherapy, immune modulating factors, and gene therapy. Although these options hold promise, the optimal treatment strategy for malignant pleural mesothelioma remains to be determined.