The appropriate function of insulin-producing pancreatic β-cells is crucial for the regulation of glucose homeostasis, and its impairment leads to diabetes mellitus, the most common metabolic disorder in man. In addition to glucose, the major nutrient factor, inputs from the nervous system, humoral components, and cell-cell communication within the islet of Langerhans act together to guarantee the release of appropriate amounts of insulin in response to changes in blood glucose levels. Data obtained within the past decade in several laboratories have revitalized controversy over the autocrine feedback action of secreted insulin on β-cell function. Although insulin historically has been suggested to exert a negative effect on β-cells, recent data provide evidence for a positive role of insulin in transcription, translation, ion flux, insulin secretion, proliferation, and β-cell survival. Current insights on the role of insulin on pancreatic β-cell function are discussed.