The existence of clinically successful cell therapies (islet transplantation) for type 1 diabetes has stoked a keen interest in developing alternative, inexhaustible sources of insulin-producing cells. In this chapter we will broadly cover the state of the art regenerative therapies for the endocrine component of the pancreas, from stem cells to transdifferentiation. In particular, we will review the basics of pancreatic development, whose recapitulation remains the subject of a plethora of in vitro differentiation strategies using both embryonic and adult stem cells. Then we will examine the leading theories about the cellular and molecular mechanisms behind the in vivo regeneration of the organ that is observed under specific circumstances, as well as the purported ability of some tissues to turn into pancreatic endocrine cells when subjected to specific interventions (transdifferentiation). Finally, we will conclude with a general overview of the remaining challenges and clinical perspectives of all the above strategies, with a special emphasis on the immunological hurdles to be overcome for these approaches to find their way to standard clinical practice.