Genomic sequences have been determined for a number of strains of Helicobacter pylori (H. pylori) and related bacteria. With the development of microarray analysis and the wide use of subtractive hybridization techniques, comparative studies have been carried out with respect to the interstrain differences between H. pylori and inter-species differences in the genome of related bacteria. It was found that the core genome of H. pylori constitutes 1111 genes that are determinants of the species properties. A great pool of auxillary genes are mainly from the categories of cag pathogenicity islands, outer membrane proteins, restriction-modification system and hypothetical proteins of unknown function. Persistence of H. pylori in the human stomach leads to the diversification of the genome. Comparative genomics suggest that a host jump has occurs from humans to felines. Candidate genes specific for the development of the gastric diseases were identified. With the aid of proteomics, population genetics and other molecular methods, future comparative genomic studies would dramatically promote our understanding of the evolution, pathogenesis and microbiology of H. pylori.