It is now well established that the microbiota have a profound influence on the outcome of enteric infections, including those caused by Salmonella and pathogenic E. coli. However, the mechanisms behind these effects are still poorly understood. We have begun to closely examine the interactions between microbiota and the etneric pathogens Salmonella and Citrobacter rodentium (as a model for EPEC and EHEC). We have found significant cross talk between the pathogens, the microbiota and their metabolites, and host responses, including effects on pathogen virulence systems, affecting gene expression. This has led to the identification of genes that are known to impact virulence, yet their mechanisms are undefined. Collectively, by better understanding the crosstalk between microbiota and enteric pathogens will not only increase our understanding of pathogenesis, but provide potential future methods to develop novel preventatives.