Salmonella infections are a serious medical and veterinary problem world-wide and cause concern in the food industry. Vaccination is an effective tool for the prevention of Salmonella infections. Host resistance to Salmonella relies initially on the production of inflammatory cytokines leading to the infiltration of activated inflammatory cells in the tissues. Thereafter, T- and B-cell dependent specific immunity develops allowing the clearance of Salmonella microorganisms from the tissues and the establishment of long-lasting acquired immunity to re-infection. The increased resistance that develops after primary infection/ vaccination requires T-cells, cytokines such as IFNγ, TNFα and IL12 in addition to opsonising antibody. However, for reasons that are not fully understood, seroconversion and/or the presence of detectable T-cell memory do not always correlate with the development of acquired resistance to infection. Whole-cell killed vaccines and subunit vaccines are used in the prevention of Salmonella infection in animals and in humans with variable results. A number of early live Salmonella vaccines derived empirically by chemical or u.v. mutagenesis proved to be immunogenic and protective and are still in use despite the need for repeated parenteral administration. Recent progress in the knowledge of the genetics of Salmonella virulence and modern recombinant DNA technology offers the possibility to introduce multiple, defined, attenuating and irreversible mutations into the bacterial genome. This has recently allowed the development of Salmonella strains devoid of significant side effects, but still capable of inducing solid immunity after single oral administration. Live attenuated Salmonella vaccines have been used for the expression of heterologous antigens/proteins that can be successfully delivered to the immune system. Furthermore, Salmonella can transfer plasmids encoding foreign antigens under the control of eukaryotic promoters (DNA vaccines) to antigen-presenting preseiiting cells resulting in targeted delivery of DNA vaccines to these cells. Despite the great recent advances in the development of Salmonella vaccines, a large proportion of the work has been conducted in laboratory rodents and more research in other animal species is required.