The intestinal epithelium provides a barrier between a variety of luminal antigens and provides the components of intestinal innate and adaptive immunity. It is crucial that at this interface, the epithelial cell layer and the components of the intestinal immunity interact with dietary and bacterial antigens in a regulated way to maintain homeostasis. Failure to tightly control immune reactions can be detrimental and result in inflammation. In the current review, we described the regulatory mechanisms controlling host–immune homeostasis and the role of regulatory CD4+ T cells, with a special emphasis in the regulatory T-cell subsets (Tregs). Furthermore, the participation of innate cell cross-talk in the polarization of intestinal immune responses is also evaluated. Finally, the recent characterization of host responses to normal commensal flora, the role of bacteria and bacterial factors in the maintenance of immunomodulation, and the disruption of this balance by bacterial enteric pathogens is also summarized.