Malignant Mesothelioma is an aggressive and fatal type of tumor. The incidence of mesothelioma has increased in the past 30 years and is now common as male cancers of the liver, bone and bladder, especially in Europe and Australia. The main risk factor is asbestos exposure even if other co-factor, such as simian virus 40 (SV40) could be implied in its etiology. Unfortunately, its incidence is expected to continue to increase for the next decades, also in rapidly industrializing countries, such as India, where it is not recognised as an occupational disease. Furthermore, some disastrous events, such as the World Trade Center Disaster, may contribute to increase future risk for mesothelioma. The treatment-resistant phenotype of mesothelioma is largely due to its ability to escape from the highly regulated apoptotic machinery. The understanding of the molecular mechanisms responsible of the malignant mesothelioma resistance to apoptosis is now advancing, allowing developing new therapeutic strategies to change the natural history and improve survival of patients. This review gives an overview of the main anti-apoptotic strategies devised by malignant mesothelioma and the therapeutic implication and opportunities for this cancer.