Pancreatic carcinoma is one of the most enigmatic and aggressive malignant disease facing oncologists. A precocious propensity to spread along peripancreatic neurons and lymphatic channels conspires with the limited activity of standard chemotherapeutic agents and the inability to deliver large doses of radiotherapy to the upper abdomen, leaving radical surgical resection as the primary treatment capable of influencing long-term survival. Theoretically, when the tumor is small and confined to the pancreas, adequate locoregional control is possible by radical resection of the tumor, lymph nodes, peripancreatic neurons, and surrounding soft tissue. Realistically, at the time of initial diagnosis, 50% of patients have distant metastases to the liver or peritoneal surface, and more than 80% of the remaining patients have locally advanced tumors. Fewer than 10% of all patients with a small pancreatic adenocarcinoma confined to the pancreas are candidates for cure by use of radical resection as the sole treatment modality. Given these sobering statistics on the late presentation of this tumor, it is not surprising that, even after radical resection, the overall median survival time is only 18 to 20 months and the overall 5-year survival is approximately 10%. These dismal results led to a call in the early 1970s for abandonment of radical therapy in this disease and for treatment of all patients with palliative care only. These statistics are discouraging, but over the last 10 years a therapeutic renaissance has erupted. This resurgence has been driven by surgeons performing pancreaticoduodenectomy with low perioperative mortality rates and excellent functional results. It has been fueled by the use of adjuvant and neoadjuvant chemoradiotherapy protocols. Improved radiographic imaging techniques such as endoscopic retrograde cholangiopancreatography, helical computed tomography scan, and endoscopic ultrasonography are beginning to show promise in facilitating an earlier diagnosis and in providing highly accurate tumor staging without operation. It is hoped that recent observations on the molecular genetics of pancreatic adenocarcinoma will lead to a better understanding of tumor biology, which in turn should result in a more rational application of new diagnostic and therapeutic strategies. Effective percutaneous, endoscopic, and laparoscopic techniques have been developed concomitant with the recent advances in radiographic and endoscopic imaging. These minimally invasive options can now provide meaningful, long-lasting palliation and improved quality of life for the large number of patients with unresectable or metastatic disease who have no other treatment options. The therapeutic nihilism so pervasive in previous decades has no place in the contemporary treatment of patients with pancreatic adenocarcinoma. True long-term survival seems possible for a growing proportion of patients, and minimally invasive, effective palliation is achievable in the vast majority of patients. It is only through aggressive recruitment of patients for treatment, application of novel diagnostic and therapeutic protocols, and further laboratory investigation into the biology of pancreatic cancer that the momentum of the last decade toward improved outcome and quality of life can be sustained.