Traveler's diarrhea is usually an acute, self-limited illness; however, in some patients, enteric symptoms can persist for weeks, months, or years. It has been estimated that up to 3% of patients with traveler's diarrhea have symptoms for >30 days. The differential diagnosis includes persistent infection, coinfection, temporary postinfection phenomena, or malabsorptive syndromes. Once these possibilities are excluded, and if symptoms persist, a diagnosis of postinfectious irritable bowel syndrome (PI-IBS) becomes more likely. PI-IBS has recently become a topic of considerable clinical and investigative interest, because evidence validating it as a diagnosis and elucidating its pathophysiological mechanisms has accumulated. Epidemiological evidence suggests that PI-IBS is a relatively common sequela of acute gastroenteritis. Experimental evidence suggests that chronic inflammation following acute bacterial infection has a pathophysiological role in the development of PI-IBS. A fuller understanding of these pathophysiological mechanisms will lead to a more directed therapeutic approach and, perhaps, a reevaluation of prophylaxis for traveler's diarrhea as a means of primary prevention of PI-IBS.