Malignant pleural mesothelioma is an aggressive tumor of serosal surfaces resistant to many current treatment options. This article will provide a comprehensive discussion of the latest developments in the treatment of malignant pleural mesothelioma, with a focus on radiation therapy. We will discuss the role of radiotherapy as a prophylactic, palliative and potentially curative treatment of malignant pleural mesothelioma. An update will be provided of the latest clinical trials including new treatment.