Pancreatic duct carcinoma remains a common disease with a poor prognosis. More than 30,000 Americans will die of the disease in 2004, making it the fourth leading cause of cancer death. Despite significant advances in the treatment of many other human tumors, the 5-year survival rate for persons diagnosed with pancreatic cancer has not changed in decades and remains <5%. This is due both to the inherently aggressive biology of the disease and to its late diagnosis in most cases. Surgical resection of localized disease remains the only hope for cure of pancreatic cancer. Over the past 2 decades, significant advances in diagnostic imaging, staging, surgical technique, and perioperative care have led to marked improvement in the surgical management of pancreatic cancer patients. Operative mortality rates for pancreaticoduodenectomy are now <5% at major centers, and the average length of hospital stay has been reduced to <2 weeks. Improvements in patient outcome after pancreatic cancer surgery have made possible, for the first time, the design and conduct of large adjuvant therapy studies in pancreatic cancer. Such clinical trials are critical for improving outcomes for pancreatic cancer patients.