The recent emergence of food-borne pathogens, such as Salmonella enterica serotype Enteritidis (S. enteritidis) and Escherichia coli O157:H7, has generated increasing interest in how infectious diseases can invade, persist and spread within new host populations. To alter their host range pathogens require adaptations, which ensure their circulation in a new animal population. Adaptations for circulation in different populations of vertebrate hosts seem to have been acquired multiple times within the genus Salmonella because extant Salmonella serotypes differ greatly with regard to host range. In this article, mechanisms involved in host adaptation are deduced by considering the influence of the host immune response on circulation of Salmonella serotypes within populations of vertebrate animals. This approach contributes to the identification of genes involved in host adaptation and provides new insights into the emergence of food-borne pathogens.