For nearly 100 years, developmental biologists have utilized fate mapping to understand the contributions of progenitor populations to organogenesis. More recently, Cre-Lox technology has allowed genetic fate mapping in adult mice, clarifying cell hierarchies in adult kidney disease models. In ischemia–reperfusion injury, genetic labeling of epithelial cells has demonstrated that intrinsic epithelial cells are responsible for nephron repair and not an interstitial or other non-epithelial cell type. In fibrotic kidney injury, fate mapping techniques have strongly challenged the theory that epithelial cells traverse the basement membrane to become myofibroblasts in a process of epithelial-to-mesenchymal transition and also indicate that interstitial pericytes/perivascular fibroblasts are the authentic myofibroblast progenitor pool. This mini review will summarize the fate mapping approach in mice, convey recent developments in kidney disease models, and outline future opportunities to apply this technology to better understand the cellular mechanisms of adult kidney homeostasis and disease.