Pain is one of the most troubling symptoms for many of the over 10 million cancer patients in America. For many patients, traditional medications and treatments are not effective and they are severely debilitated by their pain, causing needless suffering at the end of life. Pancreatic cancer in particular is associated with severe, unrelenting pain that may not be responsive to opioids and other medication therapies. Celiac plexus neurolysis is a procedure with demonstrated efficacy for patients with visceral pain arising from an upper abdominal malignancy. Although a variety of techniques exist, efficacy is generally achieved in 70-90% of patients regardless of technique. Most providers will perform a diagnostic block of the celiac plexus to ensure benefit before proceeding to the neurolytic block; however, others advocate proceeding directly to the neurolytic block. In this article, we review the techniques for chemical neurolysis of the celiac plexus, discuss the literature supporting the different approaches, and discuss factors that may influence the decision to proceed with diagnostic block prior to the neurolytic procedure. © 2011 Elsevier Inc.