Most patients with traveler's diarrhea can be efficiently treated with available pharmacological agents. A more difficult problem is the persistent diarrhea (lasting > or = 14 days) that occurs in approximately 3% of travelers who have acute diarrhea. In the initial evaluation of these patients, ideally three stool samples should be obtained for examination for pathogens. If an agent is not identified or the patient has not responded to specific therapy, he or she may be empirically treated with an antimicrobial drug directed toward common bacterial enteropathogens, if such treatment has not already been administered. For those patients whose conditions do not respond, antiprotozoal therapy may be employed empirically. If diarrhea continues, then an endoscopic evaluation is indicated, and specific treatment can be given if an agent or condition is identified. A proportion of patients will continue to have diarrhea following empirical therapy and a gastroenterologic workup. These individuals are best given symptomatic treatment and reassured that the prognosis is good.