Diarrhea is the major health problem in travelers to developing countries. Travel to high-risk areas in Latin America, Africa, the Middle East, and Asia is associated with diarrhea rates of 20% to 50%. The syndrome is caused by an infection acquired by ingesting fecally contaminated food or beverages. Escherichia coli, a common species of enteric bacteria, is the leading pathogen, although a host of other bacteria, viruses, and protozoa have been implicated in some cases. Prudent dietary and hygienic practices should be followed, and they will prevent some, but not all, diarrhea. Antimicrobial agents are not recommended for prevention of TD. Such widespread usage in millions of travelers would cause many side effects, including some severe ones, while preventing a disease that has had no reported mortality. Instead of universal antimicrobial prophylaxis, a more sensible approach is rapid institution of effective treatment that can shorten the disease to 30 hours or less in most people. For mild diarrhea, an antimotility drug such as diphenoxylate or loperamide could be taken. Alternatively, bismuth subsalicylate, which works somewhat slower, can be used. For more severe diarrhea, an antimicrobial drug may be used for treatment, and trimethoprim-sulfamethoxazole, trimethoprim alone, and doxycycline are among the choices. These drugs could be carried by the traveler for use in the event of illness. Oral rehydration should be instituted when necessary. The millions of Americans who travel annually to developing countries and their physicians must be warned of the potential risks of prophylactic antimicrobial drugs, with the attendant side effects in otherwise healthy individuals, and should be informed of the alternative method of prompt, effective treatment of diarrhea.