Regenerative medicine could provide treatments for heart disease but a source of cells capable of regenerating cardiac muscle cells remains elusive. One possible source is the epicardium, but lineage-tracing studies have produced conflicting results about the extent to which epicardial cells act as a natural source of cardiac muscle during development. Now, on p. 2895, Kazu Kikuchi and co-workers show that, in zebrafish, epicardial cells adopt only non-myocardial fates during heart development and also during heart regeneration, which is a naturally occurring process in adult zebrafish. The researchers identify the transcription factor gene tcf21 as a specific epicardial marker that is expressed throughout heart development and regeneration. Using tcf21 regulatory sequences and inducible Cre recombinase technology, they show that larval or adult cells labelled by tcf21 expression give rise to adult epicardial and perivascular cells during heart development and regeneration but do not differentiate into cardiomyocytes during either form of cardiogenesis. Thus, in zebrafish, natural epicardial fates are limited to non-myocardial cell types.