Malignant pleural mesothelioma (MPM) is a primary and locally aggressive tumor of the pleura. A well defined causal relationship with asbestos exposure, and an overwhelming media interest in the use of asbestos in industrialized countries after World War II, has produced a high level of awareness of this disease. With a peak incidence of MPM expected in Europe, Australia, and the US within the next 15 years, and the failure of current treatment approaches to offer long-term survival and improve quality of life, new therapeutic regimens are warranted. The effects of surgery in terms of survival and symptomatic relief have yet to be defined because of a lack of randomized trials. The role of radiotherapy in the treatment of MPM remains controversial, as the radiosensitivity of malignant mesothelial cells is modest. MPM response to chemotherapy is comparatively poor. The combination of pemetrexed and cisplatin chemotherapy has achieved the best objective responses. Presently, a multimodal approach is considered to be the cornerstone of treatment of MPM. Important ongoing international and national trials are addressing the roles of chemotherapy (e.g. the EAP and MS01 trial), radical surgery (e.g. the MARS trial) and radiotherapy (e.g. the SAKK group phase III study).