Pain in chronic pancreatitis (CP) shows similarities with other visceral pain syndromes (ie., inflammatory bowel disease and esophagitis), which should thus be managed in a similar fashion. Typical causes of CP pain include increased intrapancreatic pressure, pancreatic inflammation and pancreatic/extrapancreatic complications. Unfortunately, CP pain continues to be a major clinical challenge. It is recognized that ongoing pain may induce altered central pain processing, eg., central sensitization or pro-nociceptive pain modulation. When this is present conventional pain treatment targeting the nociceptive focus, eg., opioid analgesia or surgical/endoscopic intervention, often fails even if technically successful. If central nervous system pain processing is altered, specific treatment targeting these changes should be instituted (eg., gabapentinoids, ketamine or tricyclic antidepressants). Suitable tools are now available to make altered central processing visible, including quantitative sensory testing, electroencephalograpy and (functional) magnetic resonance imaging. These techniques are potentially clinically useful diagnostic tools to analyze central pain processing and thus define optimum management approaches for pain in CP and other visceral pain syndromes. The present review proposes a systematic mechanism-orientated approach to pain management in CP based on a holistic view of the mechanisms involved. Future research should address the circumstances under which central nervous system pain processing changes in CP, and how this is influenced by ongoing nociceptive input and therapies. Thus we hope to predict which patients are at risk for developing chronic pain or not responding to therapy, leading to improved treatment of chronic pain in CP and other visceral pain disorders.