Adenocarcinoma of the exocrine pancreas is one of the most refractory neoplasms to medical treatment. Although of marginal value, 5-fluorouracil (5-FU) alone or in combination with other agents or modalities has been the standard surgical adjuvant approach to localized unresectable tumor as well as the standard treatment for disseminated pancreatic cancer. Recently, a new chemotherapeutic agent, gemcitabine, has been shown to be somewhat more effective than 5-FU against metastatic pancreatic cancer. Treatment with gemcitabine usually results in a greater likelihood of objective response and better symptom control than treatment with 5-FU or drug combinations that include 5-FU. However, treatment with gemcitabine does not improve overall survival of patients with disseminated neoplasm. Newer promising agents such as 9-nitrocamptothecin have recently entered clinical trials, and novel modalities (e.g., gene therapy) are nearing full-scale clinical trial. There are reasons to believe that these and other new initiatives may soon significantly improve the medical management of adenocarcinoma of the exocrine pancreas.