Since 1935, when Whipple originally described the removal of periampullary tumors, both the surgical method and the outcome associated with it have changed extensively. The mortality rates associated with the procedure as performed today have decreased from 20% to less than 5%; the 5-year survival rate after resection of pancreatic cancer has increased from 3.5% to more than 20% in some studies. These improvements are the result of improved perioperative care and the numerous modifications and technical refinements to the procedure itself. The most important determinants of long-term survival, however, relate to the biology of the tumor. Unfortunately, most pancreatic cancers are diagnosed at an advanced stage and are often unresectable. In this setting, any surgical intervention will be purely palliative in nature. Such procedures can reduce the symptoms associated with the disease and can slightly extend survival times. Several nonoperative approaches can also offer significant palliation to patients with inoperable pancreatic cancer.