Asbestos is the principal agent in the etiology of malignant mesothelioma. However, a small proportion of people exposed to asbestos develop mesothelioma. This suggests the role of host factors in the genesis of the tumor. A genetic susceptibility is suggested by the occurrence of more mesothelioma cases among blood-related members of a single family. Such an occurrence reached about 4% in a large mesothelioma series. In some studies, mesothelioma patients showed higher prevalences of additional malignancies when compared with controls. This indicates a particular vulnerability to cancer in people with mesothelioma. Not rarely, very old persons heavily exposed to asbestos remain free from asbestos-related cancer, a fact indicating an absolute resistance to the oncogenic effects of asbestos. A relative resistance may be recognized in people severely exposed to asbestos who develop mesothelioma only after 60 years or more since the onset of the exposure. The long survivals, rarely observed among mesothelioma patients, have been attributed to a high efficiency of immune mechanisms. Mesotheliomas have been reported among people with severe immune impairment, such as acquired immunodeficiency syndrome patients or organ transplant recipients. The natural history of mesothelioma shows that a resistance to the oncogenic effects of asbestos does exist. Probably, such a resistance is due to the efficient immune mechanisms. To strengthen the defence mechanisms may represent a way for preventing mesothelioma among people exposed to asbestos.