Painful sensations from the gastrointestinal (GI) tract are common symptoms in the clinic but the etiology is often not fully understood and underlying diseases can be difficult to diagnose and treat successfully. In clinical practice, GI pain is often diffuse and pain referral to somatic structures can be the presenting symptom. In addition, concomitant symptoms from the autonomic and enteric nervous system can be present and affect the pain experience. To examine patients suffering from GI pain, basic knowledge about the GI pain system is essential and assists to explain the often complex and diverse symptoms. Information about anatomical and physiological characteristics of the GI pain system come from basic, experimental and clinical research, which have also gained insight into pain mechanisms underlying chronic GI pain. Evidence for sensitisation at the peripheral and central level of the nervous system seems to be of importance. These findings have major implication for the evaluation and treatment of patients suffering from GI pain.