The pathophysiology of irritable bowel syndrome (IBS) is believed to involve alterations in the brain-gut axis; however, the mechanisms by which these changes lead to symptoms of IBS remain poorly understood. While often considered a condition without an identified "organic" etiology, emerging evidence suggests that alterations in the gastrointestinal (GI) microbiota and altered GI immune function may play a role in the pathophysiology of IBS. These recent data suggest a plausible model in which changes in the GI microbiota and activation of the GI immune system may impinge upon the brain-gut axis, causing the alterations in GI motility and functional GI symptoms observed in patients with IBS. This review summarizes the current evidence for altered intestinal microbiota and immune function in IBS. It discusses the potential etiologic role of these factors and suggests an updated conceptual model for the pathogenesis of the disorder.