Nature Reviews Molecular Cell Biology, Published online: 11 November 2025; doi:10.1038/s41580-025-00917-1The ability to track single cells in vivo, combined with insights into chromatin structure, immune–tissue crosstalk, bioelectric and metabolic cues and quantitative modelling, is changing our understanding of how tissues are repaired and renewed. This Review discusses how signals are regulated during regeneration and future directions for a more quantitative understanding of regenerative biology.