Enteropathogenic Escherichia coli, enterohemorrhagic E. coli (O157:H7) and Citrobacter rodentium are classified as attaching and effacing (A/E) pathogens based on their ability to adhere to intestinal epithelium, destroy microvilli and induce pedestal formation at the site of infection. A/E bacterial infections also cause acute diarrheal episodes and intestinal inflammation. The use of model systems has led to an understanding of the innate immune response to A/E pathogens. The innate immune system plays a protective role, initiating a productive antibody response, directly killing bacteria and inducing repair mechanisms following tissue damage caused by infection. However, hyperactivation of the innate immune system can have negative consequences, including exacerbated tissue destruction following neutrophil infiltration. Here we review how innate immune cell types, including neutrophils, macrophages and dendritic cells, orchestrate both protective and destructive responses. Such information is crucial for the development of therapeutics that can mitigate destructive inflammatory responses while accentuating those that are protective.