Myocardial infarction (MI), involving an interruption of blood flow to a part of the heart, causes death of cardiac cells owing to ischemia. The development of therapies that promote cardiac regeneration will speed recovery and reduce the high incidence of heart failure observed after MI. Whether the Wnt signalling pathway is a valid therapeutic target has been controversial. Aisagbonhi et al. now demonstrate that canonical Wnt signalling regulates an endothelial-to-mesenchymal transition during the granulation tissue formation phase of cardiac repair after MI. Their findings suggest that the Wnt pathway could be manipulated in a temporal or cell-specific manner to improve cardiac repair after MI.