In the United States and other Western cultures, a greater number of women seek health care services for symptoms of functional pain disorders, including irritable bowel syndrome, than men. Recent clinical trials indicate that gender differences in responsiveness to drug therapy also occur. Several lines of inquiry have focused on explaining this gender-related difference due to the higher prevalence of these disorders in women. Evidence of a physiologic component is based on gender differences in gastrointestinal transit time, visceral sensitivity, central nervous system pain processing, and specific effects of estrogen and progesterone on gut function. Additional factors may play a role, including gender-related differences in neuroendocrine, autonomic nervous system, and stress reactivity, which are related to bowel function and pain. However, the link between these measures and gut motility or sensitivity remains to be clarified. Psychological characteristics, including somatization, depression, and anxiety as well as a history of sexual abuse, may also contribute to gender-related differences in the prevalence of irritable bowel syndrome. Although gender differences in the therapeutic benefit of serotonergic agents have been observed, less is known about potential differences in responsiveness to nondrug therapies for irritable bowel syndrome.