The gastrointestinal (GI) tract is a system of organs within multicellular animals which facilitates the ingestion, digestion, and absorption of food with subsequent defecation of waste. A complex arrangement of nerves and ancillary cells contributes to the sensorimotor apparatus required to subserve such essential functions that are with the exception of the extreme upper and lower ends of the GI tract normally subconscious. However, it also has the potential to provide conscious awareness of injury. Although this function can be protective, when dysregulated, particularly on a chronic basis, the same system can lead to considerable morbidity. The anatomical and molecular basis of gastrointestinal nociception, conditions associated with chronic unexplained visceral pain, and developments in treatment are presented in this review.