To date, more than 20 different vertebrate master sex-determining genes have been identified on different sex chromosomes of mammals, birds, frogs and fish. Interestingly, six of these genes are transcription factors (Dmrt1- or Sox3- related) and 13 others belong to the TGF-β signalling pathway (Amh, Amhr2, Bmpr1b, Gsdf and Gdf6). This pattern suggests that only a limited group of factors/signalling pathways are prone to become top regulators again and again. Although being clearly a subordinate member of the sex-regulatory network in mammals, the TGF-β signalling pathway made it to the top recurrently and independently. Facing this rolling wave of TGF-β signalling pathways, this review will decipher how the TGF-β signalling pathways cope with the canonical sex gene regulatory network and challenge the current evolutionary concepts accounting for the diversity of sex-determining mechanisms. This article is part of the theme issue 'Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part I)'.