Generating new β-cells de novo, or regenerating them in vivo, as a cellular therapy, is becoming more tenable as a realistic goal for treatment of the devastating disease of diabetes. One suitable approach towards generating β-cells is to use -combinations of instructive and permissive cues to induce the transdifferentiation of terminally differentiated cell types into functional β-cells, which is called -reprogramming. Interesting cellular transformations reported recently during development and regeneration suggest that a wide variety of differentiated cell types in the human body may be amenable to such reprogramming. In this chapter, we highlight findings and potential approaches using cell types that are developmentally related to β-cells, and the known molecular players that may be used to control β-cell-directed transdifferentiation. Further investigation with genetic model systems, coupled with the translation to clinically sound reprogramming methods, could lead to efficient reprogramming of specific cell types, with a massive impact on human health.