The potential of stem cell therapies for the treatment of diabetes has been the cornerstone for successful political action, fundraising and academic research programs. How can these lofty goals be translated? Clinical translation of stem cell therapies for diabetes requires unraveling the underlying biology of pancreatic development and islet function, and then recapitulating development in a defined, scalable and commercially viable manner. The b-cell or surrogate b-cell product must be safe, and must secrete insulin in a physiologically appropriate response to glucose. Xenotransplantation of pig islets would address the shortage of human cadaveric donor islets and would be an alternative to b-cells derived from human pluripotent stem cells. Stem cell-derived b-cells represent a cell replacement therapy for Type 1 diabetes (T1D) and for severe Type 2 diabetes (T2D).