Zebrafish have a remarkable capacity to regenerate and, as such, are being used increasingly to study stem cells and organ regeneration. Here, Chen-Hui Chen, Kenneth Poss and colleagues establish a luciferase-based approach for visualising stem cells and regeneration in adult zebrafish (p. 4988). The researchers generate several transgenic lines that enable ubiquitous or tissue-specific expression of both firefly luciferase and mCherry. They show that, unlike the fluorescence signal, bioluminescence in these lines, which they term zebraflash, readily penetrates through adult tissues and can easily be detected. Using the cardiac zebraflash line, they demonstrate that this approach can be used to monitor the extent of heart injury and subsequent regeneration in animals in a non-invasive and high-throughput manner. Furthermore, they report, this approach can be used to detect quantitatively the progeny of engrafted stem cells in recipient animals at high spatial resolution. This methodology, along with the transgenic lines presented here, offer a valuable resource for the study of stem cells and regeneration.