Endocrine cell differentiation in the pancreas must be tightly controlled to produce appropriate numbers of each endocrine cell type in the islets. Dysregulation of this process can cause severe physiological problems – diabetes, associated with loss of β-cell generation or function, being the most obvious example. One transcription factor known to be involved in β-cell differentiation is Mnx1, mutation of which is associated with neonatal diabetes. By inactivating Mnx1 in either endocrine progenitors or β-cells, Fong Cheng Pan and co-workers have provided insights into the roles of this key regulator in mouse (p. 3637). They find that Mnx1 acts as a lineage specification factor: upon its depletion, β-cells fail to differentiate but δ-cell number is increased. Mnx1 is also needed for β-cell maintenance: mutants show extensive β- to δ-cell transdifferentiation. Intriguingly, the authors identify a small population of escaper β-cells in which Mnx1 has not been depleted, allowing expansion and differentiation; these cells then show enhanced proliferation and are able to restore (and in fact surpass) the normal β-cell number and function in the adult. Together, these data demonstrate that Mnx1 plays multiple important roles in endocrine pancreas development and function, and highlight potential mechanisms of compensation for β-cell loss.