Acute diarrhea associated with international travel is commonly caused by enterotoxigenic Escherichia coli, enteroaggregative E. coli, or noroviruses. Early studies to define these enteropathogens took place at the University of Maryland during the Theodore E. Woodward years. Although a reduction in the rate of diarrhea may be possible through avoidance of foods and beverages likely to be contaminated, a more effective preventive strategy is to administer nonabsorbed (<0.4%) rifaximin each day during trips to areas where the risk of traveler's diarrhea is high (i.e., high-risk areas). For the self-treatment of diarrhea that occurs during travel, all persons planning trips to high-risk areas should take with them medication with expected activity against the prevalent bacterial enteropathogens: rifaximin (for the treatment of common afebrile, nondysenteric diarrhea), a fluoroquinolone, or azithromycin. Further study is needed to determine whether it is possible to avoid important morbidity associated with diarrhea and the development of postinfectious irritable bowel syndrome with chemoprophylaxis and/or early effective treatment.