The ability of pathogenic bacteria to survive in the face of host defense systems is intimately linked to virulence. This is exemplified by gastrointestinal pathogens that must survive exposure to extreme acid conditions within the stomach and organic acid conditions within the small intestine. These organisms have evolved complex systems to respond to acid stress, and recent work has revealed new genetic components involved in survival and virulence. Here, we review recent work on four gastrointestinal pathogens, focusing on studies that reveal both acid-inducible resistance systems and inherent (basal state) acid-resistance systems.