A detailed description of recent advances in the management of patients with Zollinger-Ellison syndrome (ZES) is presented. The clinical presentation is reviewed, and newer diagnostic tools, both preoperative and intraoperative, are discussed. An update on surgical management is presented, including indications for abdominal exploration, intraoperative localization techniques, surgical excision, and the approach to patients with metastases or in whom no tumor is found. New strategies in the medical management of ZES also are reviewed. An update on patient survival is presented, and a review of the management of patients with multiple endocrine neoplasia type 1 and ZES is discussed.