Acute diarrheal illnesses in nontravelers are common and represent a significant health and economic burden in the United States and other developed countries. The likelihood of experiencing diarrhea is increased many fold during travel to developing countries. Extensive overlap exists in the pathogens that cause diarrhea in travelers and nontravelers, although proportions differ and show variation by geographic area and by season, and they change over time. Rates of infection are highest in infants and young children, in whom viral pathogens predominate. Person-to-person transmission may account for more than one-half of cases. In contrast, in many studies, bacterial infections predominate in travelers, who often acquire infection from contaminated food and water. Because of the globalization of the food supply, clinicians in developed countries should expect to continue to see sporadic cases and outbreaks of diarrhea caused by unusual pathogens, such as Cyclospora species.