Irritable bowel syndrome (IBS) is a common functional bowel disorder characterized by abdominal pain and change in defecation pattern. This review addresses the topic of possible sex (genetic, biological) and gender (experiential, perceptual) differences in individuals with and without IBS. Several observations make the topic important. First, there is a predominance of women as compared to men who seek health care services for IBS in the United States and other industrialized societies. Second, menstrual cycle-linked differences are observed in IBS symptom reports. Third, women with IBS tend to report greater problems with constipation and nongastrointestinal complaints associated with IBS. Fourth, serotonin (5-HT3) receptor antagonist and 5-HT4 partial agonist drugs appear to more effectively diminish reports of bowel pattern disruption in women with IBS as compared to men. This review examines sex and gender modulation of gastrointestinal motility and transit, visceral pain sensitivity, autonomic nervous system function, serotonin biochemistry, and differences in health care-seeking behavior for IBS.