Animal models are essential to further our understanding of the pathogenesis, treatment and prevention of infectious diseases. A major impediment to the development of relevant animal models, however, is the specificity of many pathogens for particular hosts. This means that human pathogens often fail to infect convenient laboratory animals or that they fail to cause the same disease in animals that they do in humans. The compromises that researchers make when dealing with this problem can lead to erroneous conclusions that represent wasted money and time, and potentially lead to adverse publicity regarding the use of animals in research. To address these issues we must ensure that animal models are reliable and meaningful. One strategy is to infect laboratory animals with pathogens that are equivalent to those from humans, such enterotoxigenic E. coli from mice and enteropathogenic E. coli from rabbits. Another strategy is to use the tools of molecular microbiology to manipulate bacteria or their hosts to overcome or exploit species barriers.