During heart development, proliferation of cardiomyocytes (CMs) must be tightly controlled to determine organ size, and different regions of the heart show differential proliferation rates. How is CM proliferation regulated in space and time, and how might the mechanisms regulating tissue growth be harnessed for clinical applications? Ibrahim Domian and co-workers investigate the role of Wnt/β-catenin signalling in regulating CM proliferation, using in vitro stem cell culture and in vivo approaches (p. 4165). They find that canonical Wnt signalling promotes proliferation of CMs derived from mouse embryonic stem cells (ESCs) or from induced pluripotent stem cells, and, importantly, of human ESC-derived CMs. Furthermore, they show that differential Wnt pathway activity likely underlies the differential proliferation rates of trabecular versus compact myocardium in the developing mouse heart in vivo. The effects of Wnt signalling on CM proliferation provides a potential method for generating large numbers of CMs in culture, which could be used for drug screening or regenerative therapy approaches.