Genetic variation in the susceptibility of cattle to Mycobacterium bovis infection exists in differences between families and species, but not breeds. Susceptibility to M. bovis infection increases with age of cattle. Natural exposure to M. bovis or environmental mycobacteria may assist in the development of specific immunity, but there is no direct evidence for such immunological priming of tuberculosis resistance in cattle. This has, however, been demonstrated in humans and other animals. Since non-specific mechanisms have a role in protective immunity, developing an effective vaccine will be difficult, even though some protection of other species has been achieved. Immunological suppression in the periparturient period can produce anergic reactors, which may act as a constant source of infection for cattle-to-cattle transmission. Circumstantial evidence suggests that an adequate intake of mineral, vitamin and protein reduces the susceptibility of cattle. Although weather patterns have been implicated in the susceptibility of herds to M. bovis infection, there is insufficient information to determine the risk factors precisely. It is concluded that some reduction in the susceptibility of cattle to M. bovis infection can be achieved by modifications to the management system to minimize risk factors, but that a considerable amount of further research is required.