In an address delivered before the Boston Surgical Society in 1942, Whipple made the following statement: The radical operation for these tumors of the ampullary region and pancreas, based on the principle of wide, en bloc removal of the tumors, as required in modern cancer surgery, is evidently in an evolutionary stage. Many more cases, with five-year survivals, will be required before valid claims can be made for the operations as done at present. In the nearly 50 years since this address, the Whipple operation has undergone numerous modifications and technical refinements. A number of recent clinical studies clearly demonstrate that this procedure now can be performed with acceptable morbidity and mortality, and that long-term survival is possible even for patients with adenocarcinoma of the head of the pancreas. The decline in operative morbidity and mortality has been achieved largely through advances in surgical technique. Further improvements in survival for patients with periampullary tumors are likely to occur through the development of more effective adjuvant therapy and improved understanding of the biologic behavior of these tumors.