Pancreatic cancer is a systemic disease for most patients. Operations with the intent to cure may be done safely (mortality, < 3%) with shorter hospital stays. Surgery has been minimally effective as a long-term cure. Endoscopic palliation of jaundice is becoming standard practice. Common sense dictates a defined and clear role for surgery (i.e., strict patient selection criteria). Surgery is of great value for small, localized lesions; of clear value as palliative therapy when nonoperative measures fail; and perhaps best applied after neoadjuvant chemoradiotherapy. Surgery is just part of the armamentarium available to treat pancreatic cancer. Novel systemic therapies, including chemotherapy, immunotherapy, and so-called targeted therapies, are becoming increasingly valuable in the management of this systemic disease and are discussed in detail in other articles in this issue.