The islets of Langerhans play a major role in control of metabolic fuel homeostasis. The rapid increase in incidence of diabetes worldwide has spurred renewed interest in islet cell biology. However, gaining a detailed understanding of islet function at a molecular and biochemical level has been complicated by the difficulty and high cost associated with isolation of pancreatic islets. Until recently, islet-derived cell lines have represented sub-optimal surrogates for primary cells for functional studies due to their undifferentiated or unstable phenotypic features. New approaches have resulted in isolation and characterization of rodent insulinoma cell lines that retain many key functional attributes of normal islets and have become useful tools in the study of islet cell biology.