Infections of the human intestinal tract with foodborne and waterborne pathogens are among the leading causes of morbidity and death in the world. Upon ingestion, such pathogens commonly pass through the stomach in sufficient numbers to establish infection in the small intestine or colon. The subsequent interactions with the host depend critically on the particular pathogen, ranging from mere presence in the intestinal lumen and minimal interaction with the epithelium to highly mucosal invasive with rapid systemic spread. This article addresses the morphological and molecular changes that occur in the intestinal mucosa after infection with a selected yet representative spectrum of enteric pathogens, ranging from luminally restricted but epithelial adherent, epithelial invasive, to mucosally invasive, with a focus on intestinal epithelial responses.