Chronic pancreatitis (CP) is a progressive inflammatory condition of the pancreas resulting in irreversible structural damage, exocrine and endocrine dysfunction, and chronic abdominal pain—severely impacting patients’ quality of life. Pain, frequently refractory to medical therapy and requiring escalating use of opioids, is the most common and debilitating symptom. For patients with hereditary pancreatitis and for those for whom previous traditional operations have failed, total pancreatectomy with autologous islet cell transplantation may offer improvement or resolution of abdominal pain in over 70% of patients. Resolution of pain after surgery is immediate for a small subset of patients but typically requires multiple months for the majority of patients. Management of pain in the immediate postoperative period and longer term requires the collaboration of a multidisciplinary pain management team including surgeons and pain specialists.