Recent interest has focused on sex-related differences in irritable bowel syndrome (IBS) physiology and treatment responsiveness to novel pharmacologic therapies. Similar to a variety of other chronic pain conditions and certain affective disorders, IBS is more prevalent amongst women, both in population-based studies as well as in clinic-based surveys. Non-painful gastrointestinal symptoms, constipation and somatic discomfort are more commonly reported by female IBS patients. While perceptual differences to rectosigmoid stimulation are only observed following repeated noxious stimulation of the gut, sex-related differences in certain sympathetic nervous system (SNS) responses to rectosigmoid stimulation are consistently seen. Consistent with experimental findings in animals, current evidence is consistent with a pathophysiological model which emphasizes sex-related differences in autonomic and antinociceptive responses to certain visceral stimuli.