Human hearts do not regenerate after a heart attack because adult mammalian cardiomyocytes proliferate poorly in response to injury. By contrast, zebrafish regenerate heart muscle after trauma by inducing cardiomyocyte proliferation. Studies of zebrafish heart regeneration might, therefore, identify ways to repair damaged human hearts. Here (p. 660), Wen-Yee Choi and co-workers develop a surrogate model for zebrafish heart regeneration that uses fluorescent ubiquitylation-based cell cycle indicator (FUCCI) technology to visualise cardiomyocyte proliferation in live zebrafish embryos. The researchers generate transgenic lines in which heart-specific promoters drive the expression of G1 and S/G2/M FUCCI probes and use these lines to identify several small molecules that alter cardiomyocyte proliferation during heart development. These molecules act via the Hedgehog, IGF or TGFβ signalling pathways, they report. Moreover, the researchers show, the same pathways are activated in regenerating zebrafish cardiomyocytes, and their pharmacological manipulation alters cardiomyocyte proliferation during adult heart regeneration. Future use of this new screening system may identify molecules with the potential to improve human heart regeneration.