Molecular studies are shedding new light on the pathogenesis of human typhoid fever, which is still a very common disease in developing countries. For example, the total genome DNA sequence has recently been determined for a multiple-drug-resistant Salmonella typhi, the serotype that is the cause of typhoid fever. The genome sequence showed many distinguishing features, including dusters of S typhi specific genes and a large number - over 200 - of pseudogenes. This information, together with other molecular studies, has provided vital clues in several important areas of typhoid biology. We have new insights into the mechanisms underpinning the human host specificity of S typhi, and have exploitable new routes to improved diagnostics and a better understanding of the epidemiology of the disease.