The recent advent of induced pluripotent stem cells (iPSCs) has transformed our ability to study the earliest stages of embryonic development, especially in comparative mammal species for which embryonic stem cells are not available. Our research uses iPSCs from domestic and native species to address clinical problems and to explore questions in developmental and evolutionary biology. iPSCs from the platypus and Tasmanian devil have allowed us to investigate, for the first time, the genes and regulatory mechanisms involved in establishing pluripotency in these evolutionarily divergent mammals.