Identifying methods by which pancreatic β-cells can be produced is of major therapeutic importance. Whether there are adult pancreatic cells with the potential to make new β-cells is a matter of much debate. During embryonic development, the transcription factor Ptf1a initially marks multipotent progenitors, before becoming restricted to acinar cells. Here (p. 751), Christopher Wright and colleagues test whether mature Ptf1a-expressing cells can regain multipotentiality upon injury by labelling Ptf1a-positive acinar cells in mice and following their fate after pancreatic duct ligation. Remarkably, not only do new duct cells arise from the labelled cells, but some labelled cells start to express endocrine markers and display the hallmarks of mature β-cells, suggesting transdifferentiation of acinar cells into β-cells. This process is inefficient and slow, but can be enhanced by prior ablation of endogenous β-cells. Thus, pancreatic injury appears to induce reactivation of a more embryonic-like multipotent state in Ptf1a-expressing cells, from which endocrine cells can differentiate, possibly opening up new avenues for generating β-cells.