Enteropathogenic E. coli (EPEC) interacts with intestinal epithelial cells, causing diarrhea and associated diseases. This pathogen binds to epithelial cells using sophisticated mechanisms that exploit existing epithelial signal transduction pathways and host cytoskeletal components, ultimately resulting in the bacterium resting upon a pedestal on host cell surfaces. Recent data indicates that similar mechanisms occur in vivo. EPEC interactions with host cells illustrate several principles of pathogenesis that are used by bacteria that interact with mammalian host cells.