Although neoplasms that produce gut regulatory peptides and amines can be found throughout the gastroenteropancreatic axis (excluding carcinoids), the vast majority of these lesions are found within the pancreas. Recognition of the various clinical syndromes produced by the secretions of these tumors, the development of sensitive and specific radioimmunoassays for the elaborated peptides, and development of more effective localization techniques have contributed to earlier diagnosis and marked improvement in patient care. Treatment is directed toward medical management to correct the metabolic disturbances produced by the excessive amounts of gut regulatory peptides, followed by localization and extirpation of tumor. In the presence of unresectable tumor or metastases, palliative treatment directed at reducing peptide secretion or preventing its effects by surgery, chemotherapy, hormonal therapy, and hepatic-artery embolization can produce long-term remission of symptoms. Because the majority of these tumors are malignant, the ultimate goal in successful patient management is the early detection and surgical excision of the islet cell tumor before metastases occur.