Animal models have become standard tools for the study of a wide array of human infectious diseases. Although there are no true animal reservoirs for M. tuberculosis, many different animal species are susceptible to infection with this organism and have served as valuable tools for the study of TB. The most commonly used experimental animal models of TB are the mouse, rabbit, and guinea pig. Although substantial differences in TB susceptibility and disease manifestations exist between these species, they have contributed significantly to understanding of TB immunopathogenesis, host genetic influence on infection, efficacy of antimicrobial therapy, and host/pathogen interactions that determine the outcome or severity of infection. Among the three species, mice are relatively resistant to TB infection, followed by rabbits and then guinea pigs, which are extremely vulnerable to infection. Mice are most often used in experiments on immune responses to TB infection and drug regimens against TB. Rabbits, unlike the other two animal models, develop cavitary TB and offer a means to study the factors leading to this form of the disease. Guinea pigs, due to their high susceptibility to infection, have been ideal for studies on airborne transmission and vaccine efficacy. In addition to these three species, TB research has occasionally involved non-human primates and cattle models. Current concepts in TB pathogenesis have also been derived from animal studies involving experimentally induced infections with related mycobacteria (e.g. M. bovis) whose manifestations in select animal hosts mimic human TB.