The management of patients who have unresectable or recurrent pancreatic adenocarcinoma represents a challenge to the practicing oncologist. Complications such as biliary or gastrointestinal obstruction, pain, and malnutrition must be controlled if there is to be a prospect of meaningful clinical benefit from presently available nonsurgical treatment. Although some reports have suggested favorable objective tumor response rates after combination chemotherapy, there has been no evidence from controlled clinical trials that the survival rates exceed those associated with single-agent therapy. Combined radiation therapy plus 5-fluorouracil has been shown to extend longevity in patients with locally unresectable pancreatic cancer, compared with radiation alone. Newer radiation therapy techniques, such as intraoperative electron-beam radiation therapy and the use of radiation sensitizers, are currently under investigation for patients with locally unresectable disease.