The variations in symptoms and pain perception across the menstrual cycle in a large percentage of women diagnosed with functional syndromes such as Irritable Bowel Syndrome (IBS), Painful Bladder Syndrome (PBS), and Chronic Pelvic Pain (CPP), suggests the involvement of modulation of sex steroid hormones. Our recent studies have shown that estrogen modulation of visceral inputs of primary afferent nociceptors, located in the afferent primary sensory neurons of the dorsal root ganglia (DRG), accounts for the observed changes in nociception. Patients with CPP frequently experience pain from several organs. For patients with IBS, the most common co-morbid diagnoses include PBS and CPP. Pain is strongly associated with these diseases and the lack of awareness of their pathology is further illustrated by the fact that the average time between the onset of pain and the diagnosis is three to ten years. CPP patients may initially only have pain in the pelvis, but a multitude of mechanisms involving the peripheral and central nervous systems can lead to development of painful sensations in other adjacent organs; examples include lower colonic pain associated with IBS, and other viscera such as the endometrium. In addition to the central regulation of pain, it is important to understand the new pathways in which sex steroid hormones, such as estrogen, affect visceral nociception peripherally.