The potential of cell-replacement strategies for the treatment of disorders in which a particular cell type is damaged or degenerated has prompted the search for the perfect cell source. iPSCs (induced pluripotent stem cells) stand out as very advantageous candidates thanks to their self-renewal capacity and differentiation potential, together with the possibility of generating them from autologous somatic cells with minimally invasive techniques. However, their differentiation into the required cell type, precise delivery and successful engraftment and survival in the host are still challenging subjects. We have proposed the transient reprogramming of somatic cells towards a pluripotent state in their in vivo microenvironment as a means to facilitate the regeneration of the tissue. The initial reports of in vivo reprogramming to pluripotency in the literature are reviewed and the potential clinical applications of this strategy are discussed.