Typhoid fever is an infectious disease of global distribution. Although there is a wealth of data on Salmonella typhimurium infection in the mouse and the interaction of this serovar with human cell lines in vitro, there is a relatively small amount of data on S. typhi and the pathogenesis of typhoid fever. In this review we focus on three areas: adherence to and invasion of gut epithelial cells, dissemination to systemic sites, and survival and replication within host cells. In addition, we attempt to put current salmonella research into the context of typhoid fever.