A major focus of research in the diabetes field has been the identification of a ‘source’ of insulin-secreting beta cells to enable the development of therapeutic approaches to enhance the mass of functional beta cells to cure and/or prevent the development of all forms of diabetes. While reduplication of adult beta cells is considered a major source in rodents the potential long half-life of beta cells in humans suggests alternative mechanism(s) likely play a role to maintain optimum beta cell mass to insure the blood glucose remains with the normal physiological range. This presentation will include the discussion of a series of studies that support a role for the pancreatic duct as an important source of beta cells in humans.