Zollinger-Ellison syndrome (ZES) is a rare disease. Its management concerns symptoms related to the gastric acid overproduction that characterizes the syndrome and to the gastrin-producing tumor(s) usually located in the duodenal wall and/or the endocrine pancreas. Acid hypersecretion is now controlled by the use of powerful antisecretory agents. Management of the malignant process(es) has become the primary goal of modern strategy: it aims first at curing the disease and second at prolonging patient survival by prevention of hepatic metastasis. In patients with the sporadic form of the disease and without liver metastases, it is currently possible to localize and to surgically remove the endocrine tumor(s). This progress has been made feasible by refinements in modern medical imaging. At present, however, disease cure, even in the most favorable conditions, is not be greater than 30 to 50 percent at five years. In patients with ZES integrated in the context of multiple endocrine neoplasia type I, disease cure rate is extremely low, although occasional patient survival can be as good or even better than in the sporadic group. Disseminated malignancy (liver and/or extra-abdominal lymph nodes or bone localization) remains the principal determinant of early death. Surgical treatment is usually precluded in such cases. Liver transplantation has not been successful in these patients.