Salmonella is a major foodborne pathogen of both animals and humans. This bacterium is responsible for considerable morbidity and mortality world-wide. Different serovars of this genus cause diseases ranging from self-limiting gastroenteritis to a potentially fatal systemic disease known as enteric fever. Gastrointestinal infections with Salmonella are usually self-limiting and rarely require medical intervention. Bloodstream infections, on the other hand, are often fatal even with hospitalization. This review describes the routes and underlying mechanisms of the extraintestinal dissemination of Salmonella and the chronic infections that sometimes result. It includes information on the pathogenicity islands and individual virulence factors involved in systemic dissemination as well as a discussion of the host factors that mediate susceptibility. Also, the major outbreaks of invasive Salmonella disease in the tropics are described.