During the last decade, research on attaching-effacing (A/E) bacteria/host cell interactions has revealed much of the molecular basis of colonization and lesion formation. The colonic mucosa represents the first line of defense against these pathogens, and its integrity is required to avoid translocation of bacteria or bacterial soluble factors into the infected host. Therefore, the cellular immune response to A/E pathogens plays an important role in bacterial pathogenesis since it can clear the bacteria or modulate the inflammatory processes. Data obtained from infected patients demonstrate a correlation between the production of pro-inflammatory cytokines and the severity of the disease. In vitro studies of infected epithelial cells have clearly elucidated A/E bacteria-induced host signal transduction events. However, the identification of the bacterial factors responsible for cellular activation remains a subject of controversy. Experimental studies with knock-out mice infected with Citrobacter rodentium, a rodent A/E pathogen, indicate that innate immunity is an essential component of pathogenesis. This review summarizes in vivo and in vitro evidence for the induction and potential role of the innate immune system during infection with A/E bacteria.