The developing complementary technologies of DNA microarrays and proteomics are allowing the response of bacterial pathogens to different environments to be probed at the whole genome level. Although using these technologies to analyze pathogens within a host is still in its infancy, initial studies indicate that these technologies will be valuable tools for understanding how the pathogen reacts to the in vivo microenvironment. Some bacterial pathogens have been shown to substantially modify their surface components in response to the host immune system and modify their energy metabolism and transport pathways to allow efficient growth within the host. Further detailed analyses of these responses will increase understanding of the molecular mechanisms of pathogenesis, identify new bacterial virulence factors, and aid in the design of new vaccines.