Retinoic acid receptor γ (RARγ) is expressed mainly in stem and progenitor cells and helps control whether they maintain stemness or develop. This review by Geoffrey Brown draws on haematopoiesis, embryonic development, and the generation of induced pluripotent stem cells, and shows that RARγ acts both as a transcription factor and as a co-factor, for example to Smad3, influencing Wnt/β-catenin and Notch signalling. In cancer, RARγ is oncogenic in leukaemia and in many carcinomas, including prostate cancer. Overexpression or agonism enhnces proliferation, while antagonism kills cancer cells, including cancer stem cells, with normal cells less sensitive. Retinoic acid levels are very low in patient’s prostate cancer cells, so they appear to depend on RARγ. Prof. Brown proposes RARγ antagonists against aggressive or relapsing cancers, but notes that efficacy in xenograft models and effects on normal stem cells remain to be tested.