Following a long period during which studies on the pathogenesis of salmonellosis and typhoid fever have been exclusively based on careful evaluation of clinicopathological data in infected patients and experimental infection in mice, the new tools that are now offered by molecular genetics and cell biology allow more systematic and analytical approaches. Numerous mutants have been obtained that can be assayed in selected cell assay systems such as in vitro-cultivated epithelial cells or macrophages, thus allowing to identify and characterize key virulence bacterial products as well as their eucaryotic receptors and effectors. Significant contributions have recently been made in the analysis of the mechanisms allowing invasion of the intestinal epithelium and survival and multiplication of bacteria within macrophages. However, many unsolved questions remain. It is still unclear what produces diarrhea during salmonellosis and studies on the pathogenesis of typhoid fever are still impaired by the lack of a proper animal model.