In order to infect a host, a microbe must be equipped with special properties known as virulence factors. Bacterial virulence factors are required to facilitate colonization, to survive under host defenses, and to permit multiplication inside the host. However, the possession of genes encoding virulence factors does not guarantee effective infection. There is considerable evidence that tight regulation of a given virulence factor is as important as the possession of the virulence factors themselves. Thus, an understanding of the regulation of virulence expression is fundamental to our comprehension of any infection process and can identify potential targets for disease prevention and therapy. We have summarized the lessons learned from experimental salmonellosis in terms of virulence regulation and hope to illustrate the differing requirements for gene and virulence expression.