Malignant pleural mesothelioma may be treated with surgery, radiotherapy and chemotherapy. In most patients, the treatment remains palliative with symptom relief and a moderate survival gain. Only a minority of patients with early stage mesothelioma may be cured by a multimodal approach including radical surgery, chemotherapy, and radiotherapy. We discuss the role of surgery with either radical extrapleural pleuropneumonectomy or less invasive palliative pleurectomy and decortication, and the role of radiotherapy, in which the main problem is how to deliver sufficient doses to the pleural surface, sparing radiosensitive structures such as the lung, heart, liver, and kidneys. Chemotherapeutic options are discussed with 'older' mono- and combination regimens and the new promising combination cisplatinum/pemetrexed, now the 'standard regimen' for malignant pleural mesothelioma. Experimental approaches such as hyperthermia, interferons or interleukins, and 'small molecules' or antibodies inhibiting the EGFR oder VEGF receptor are under clinical evaluation. For the majority of our patients we recommend talcum pleurodesis either by medical thoracoscopy or VATS, followed by chemotherapy with platinum/pemetrexed. Radiotherapy may be applied in case of local tumour growth. The individual therapeutic decision will depend on tumour stage, concomitant diseases, performance status, and on the patient's preference.