The ability of bacteria to mediate gene transfer has only recently been established and these observations have led to the utilization of various bacterial strains in gene therapy. The types of bacteria used include attenuated strains of Salmonella, Shigella, Listeria, and Yersinia, as well as non-pathogenic Escherichia coli. For some of these vectors, the mechanism of DNA transfer from the bacteria to the mammalian cell is not yet fully understood but their potential to deliver therapeutic molecules has been demonstrated in vitro and in vivo in experimental models. Therapeutic benefits have been observed in vaccination against infectious diseases, immunotherapy against cancer, and topical delivery of immunomodulatory cytokines in inflammatory bowel disease. In the case of attenuated Salmonella, used as a tumour-targeting vector, clinical trials in humans have demonstrated the proof of principle but they have also highlighted the need for the generation of strains with reduced toxicities and improved colonization properties. Altogether, the encouraging results obtained in the studies presented in this review justify further development of bacteria as a therapeutic vector against many types of pathology. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.