Here we discuss the neuroanatomy of extrinsic gastrointestinal (GI) afferent neurones, the relationship between structure and function and the role of afferents in disease. Three pathways connect the gut to the central nervous system: vagal afferents signal mainly from upper GI regions, pelvic afferents mainly from the colorectal region and splanchnic afferents from throughout. Vagal afferents mediate reflex regulation of gut function and behaviour, operating mainly at physiological levels. There are two major functional classes - tension receptors, responding to muscular contraction and distension, and mucosal receptors. The function of vagal endings correlates well with their anatomy: tracing studies show intramuscular arrays (IMAs) and intraganglionic laminar endings (IGLEs); IGLEs are now known to respond to tension. Functional mucosal receptors correlate with endings traced to the lamina propria. Pelvic afferents serve similar functions to vagal afferents, and additionally mediate both innocuous and noxious sensations. Splanchnic afferents comprise mucosal and stretch-sensitive afferents with low thresholds in addition to high-threshold serosal/mesenteric afferents suggesting diverse roles. IGLEs, probably of pelvic origin, have been identified recently in the rectum and respond similarly to gastric vagal IGLEs. Gastrointestinal afferents may be sensitized or inhibited by chemical mediators released from several cell types. Whether functional changes have anatomical correlates is not known, but it is likely that they underlie diseases involving visceral hypersensitivity.