The pancreatic islet is composed of three types of cells of neural crest origin, each with distinct histochemical and electromicroscopic features. Each type of cell may give rise to a benign or malignant neoplasm that usually presents with a clinical syndrome related to hypersecretion of a native or ectopic hormonal product. Diagnosis of the tumor depends most on specific assay of the hormone produced. In malignant insulinoma and Zollinger-Ellison syndrome an increase in plasma proinsulin-like component, or “big” gastrin, may be the most specific finding. The exact hormone responsible for the “pancreatic cholera” syndrome remains unknown, but biologically it is secretin-like. Treatment of the Zollinger-Ellison syndrome is removal of the end organ; direct resection of tumor is the primary form of therapy for all other islet cell neoplasms. Palliation of functioning malignancies often requires both antihormonal and anticancer chemotherapy. The use of streptozotocin and L-asparaginase to treat malignant insulinoma is reviewed.