There are about 16 million cases of typhoid fever throughout the world each year. In the October 25 Nature, Parkhill et al. report the complete genome sequence of the pathogenic culprit, Salmonella enterica serovar Typhi CT18 (Nature 2001, 413:848-852). The drug-resistant strain has a genome of 4.8 Mb containing over two hundred pseudogenes, some of which correspond to virulence genes in Salmonella typhimurium. In the same issue of Nature, McClelland et al. report the sequence of the Salmonella enterica serovar Typhimurium LT2 (Nature 2001, 413:852-856). This strain causes human gastroenteritis and provides a mouse model for typhoid fever. The gene differences between CT18 and LT2 may explain the human-restricted host range of S. typhi. CT18 has a multiple-drug-resistance plasmid and a cryptic plasmid resembling the virulence plasmid of Yersinia pestis. The LT2 strain also has a 94-kb virulence plasmid. The use of these sequences for comparative bacterial genomics (for example, comparisons with other Salmonella strains or closely-related sequenced genomes such as that of Escherichia coli) should identify genes related to host specificity and pathogenesis, and identify potential therapeutic or vaccine targets.