The surgical treatment of patients with the Zollinger-Ellison syndrome has undergone a dramatic evolution since the syndrome was originally described. It is now recognized that an aggressive surgical approach is mandatory because of the malignant potential of gastrinomas in both the sporadic and the familial forms of the syndrome. Although initially regarded as an incurable neoplasm, it is now known that complete surgical resection of gastrinomas can result in eugastrinemia even in the presence of lymph node metastases. It is now recognized that extrapancreatic gastrinomas are more common than pancreatic gastrinomas, and the most common location for an extrapancreatic gastrinoma is the duodenal wall. Major improvements in preoperative imaging and intraoperative localization techniques combined with an increased awareness of the anatomic distribution of gastrinomas have markedly increased the surgeon's ability to care for and cure patients with the Zollinger-Ellison syndrome.