Malignant pleural mesothelioma is a rare, aggressive tumor with a well-described natural history but poorly defined pathogenesis. It is strongly associated with asbestos exposure. A predominantly locally invasive disease, the success of more aggressive life-prolonging therapies has increased the potential for the development of distant metastases in survivors. Recently described new risk factors may increase the incidence of this disease in future generations, underscoring the need for a more in-depth understanding of its pathobiology. This article reviews the current body of knowledge about the occurence, distribution, presentation, and natural history of malignant pleural mesothelioma.