Muscle development is driven by a set of myogenic factors, but how these are regulated during normal development and during regeneration is unclear. Here (p. 3743), Charlotte Harken Jensen and colleagues show that delta-like 1 homolog (Dlk1), an imprinted gene, is a crucial regulator of the myogenic program in mice. They report that Dlk1-null mice exhibit impaired muscle development due to a defective myogenic transcriptional program: the myogenic genes Mef2c, Meis1 and Myod1 are suppressed in these mice. Surprisingly, however, they find that depletion of Dlk1, which is known to be re-expressed in regenerating muscle, in fact enhances muscle regeneration both in vitro and in vivo. This improved regenerative capacity in the absence of Dlk1 is associated with an enhanced myogenic program, and is not due to altered adipogenic-myogenic commitment. Together, these findings highlight a dual function for Dlk1 - as an enhancer of muscle development but as an inhibitor of muscle regeneration - and may open up new possibilities for improving muscle regeneration in human disease.