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Chronic upper abdominal pain occurs as a complication of various malignant and benign diseases including pancreatic cancer and chronic pancreatitis, and when present may contribute to lower quality of life and higher mortality. Though various pain management strategies are available as part of a multimodal approach, they are often incompletely effective and accompanied by side effects. Pain originating in upper abdominal viscera is transmitted through the celiac plexus, which is an autonomic plexus located in the retroperitoneum at the root of the celiac trunk. Direct intervention at the level of the plexus, referred to as celiac plexus block or neurolysis depending on the injectate, is a minimally invasive therapeutic strategy which has been demonstrated to decrease pain, improve function, and reduce opiate dependence. Various percutaneous techniques have been reported, but, with appropriate preprocedural planning, use of image guidance (usually computed tomography), and postprocedural care, the frequency and severity of complications is low and the success rate high regardless of approach. The main benefit of the intervention may be in reduced opiate dependence and opiate-associated side effects, which in turn improves quality of life. Celiac plexus block and neurolysis are safe and effective treatments for chronic upper abdominal pain and should be considered early in patients experiencing such symptoms.