The identity of somatic and pluripotent cells can be epigenetically reprogrammed and forced to adapt a new functional cell state by different methods and distinct combinations of exogenous factors. The aspiration to utilize such ex vivo reprogrammed pluripotent and somatic cells for therapeutic purposes necessitates understanding of the mechanisms of reprogramming and elucidating the extent of equivalence of the in vitro derived cells to their in vivo counterparts. In my presentation, I will present my group’s recent advances toward understanding these fundamental questions and further detail our ongoing efforts to generate developmentally unrestricted human naive pluripotent cells. I will conclude by highlighting new avenues for utilizing epigenetic reprogramming to naïve pluripotency for unraveling critical gene regulatory mechanisms acting during early mammalian development and highlighting prospects for new platforms for human disease and developmental modelling.