This book offers an updated review of malignant mesothelioma, including the latest advances in our understanding of its genetic control and molecular biology, as well as pre-clinical and clinical research. It also presents state-of-the-art diagnostic approaches and therapeutic options, and an open discussion on the future prospects for patient management. Malignant mesothelioma is an enormous global health problem related to asbestos exposure. Despite the best efforts of scientists and oncologists, the prognosis for those affected remains poor. Due to anatomical characteristics and non-specific symptoms, the diagnosis of mesothelioma at an early stage is often difficult, while surgery and radiotherapy are only of limited use, even if some multimodality approaches seem promising. In turn, medical treatments are sometimes successful in tumor control, but have little impact on overall survival.