The intestinal epithelium forms a single cell barrier that separates the host's internal milieu from luminal contents. This article examines the role of the intestinal epithelium as a critical component of a communications network that is essential for transmitting signals generated in response to infection with microbial pathogens to cells of the innate and acquired immune systems in the underlying intestinal mucosa. It further highlights the importance of intestinal epithelium in mediating host antimicrobial defense through the production of antimicrobial peptides of the defensin and cathelicidin families.