The pancreas has been the subject of intense research due to the debilitating diseases that result from its dysfunction. In this review, we summarize current understanding of the critical tissue interactions and intracellular regulatory events that take place during formation of the pancreas from a small cluster of cells in the foregut domain of the mouse embryo. Importantly, an understanding of principles that govern the development of this organ has equipped us with the means to manipulate both embryonic and differentiated adult cells in the context of regenerative medicine. The emerging area of lineage modulation within the adult pancreas is of particular interest, and this review summarizes recent findings that exemplify how lessons learned from development are being applied to reveal the potential of fully differentiated cells to change fate.