Pain is a common symptom of pancreatic disease and is frequently difficult to manage. Pain relief provided by narcotics is often suboptimal and is associated with significant side effects. An alternative approach to pain management in pancreatic disease is the use of celiac plexus block (CPB) or neurolysis (CPN). Originally performed by anesthesiologists and radiologists via a posterior approach, recent advances in endoscopic ultrasonography (EUS) have made this technique an attractive alternative. EUS guided celiac plexus block/neurolysis is simple to perform and avoids serious complications such as paraplegia or pneumothorax that are associated with the posterior approach. EUS guided CPN should be considered first line therapy in patients with pain due to pancreatic cancer. It provides superior pain control compared to traditional management with narcotics. A trend for improved survival in pancreatic cancer patients treated with CPN has been reported, but larger studies are needed to confirm this finding. At this time, the use of EUS guided CPB cannot be recommended as routine therapy for pain in chronic pancreatitis since only one-half of the patients experience pain reduction and the beneficial effect tends to be short lived. EUS guided CPB and CPN should be used as part of a multidisciplinary team approach for pain management.