Human salmonellosis is generally associated with Salmonella enterica from subspecies enterica (subspecies I). Acute infections can present in one of four ways: enteric fever, gastroenteritis, bacteremia, or extraintestinal focal infection. As with other infectious diseases, the course and outcome of the infection depend on a variety of factors, including the infecting organism, the inoculating dose, and the immune status and genetic background of the host. For serovarsTyphi and Paratyphi A there is a clear association between the genetic background of the serovar and systemic infection in humans. For serovars Paratyphi B and Paratyphi C, a good clinical description of the host and detailed population genetics of the pathogen are necessary before more detailed genetic studies of novel virulence factors,or host factors,can be initiated. For the nontyphoidalserovars (NTS) the situation is less clear. Serovars Typhimurium and Enteritidis are the most common within the food chain, and so the large number of invasive infections associated with these serovars is most likely due to exposure rather than to increased virulence of the pathogen. In Africa, however, a closely related group of strains of serovar Typhimurium, associated with HIV infection, may have become host adapted tohumans, suggesting that not all isolates called "Typhimurium" should be considered as a single group. Here we review current knowledge of the salmonellae for which invasive disease in humans is an important aspect of their population biology.