Diarrhea continues to be a major cause of mortality and morbidity in third world countries as well as a major symptomatic complaint in the primary care setting in the United States. The etiologic pathogen depends on an exposure history to include recent travel to foreign countries, consuming fecally contaminated water or food, prior use of antibiotics, or homosexual behavior. A careful history from patients directed at attempting to identify particular risk factors may help in making a diagnosis. Not all patients require a diagnostic workup. A large number of patients may only require oral rehydration, careful observation over time with or without use of antimotility agents. In toxic appearing patients or patients with fever, however, bloody stools, abdominal pain or tenesmus, a selective diagnostic workup is indicated. Antimicrobial treatments are not always required, some pathogens clearly call for treatment while some have less clear indications and other pathogens are not responsive to antimicrobial agents at all. Finally, one needs to remember that the differential diagnosis of acute diarrhea includes many noninfectious origins.