Importance of the field: Retinal degenerations cause blindness. One potential therapy is cell replacement. Because the human retina lacks regeneration capacity, much attention has been directed towards searching for cells that can differentiate into retinal neurons. Areas covered in this review: We discuss the possibility of using transcription factor genes to channel retinal pigment epithelial (RPE) cells' capabilities of proliferation and plasticity towards the production of retinal neurons. What the reader will gain: Experiments with chick embryos show that RPE cells in the eye, in explant, or in a dissociated cell culture can give rise to cells resembling retinal neurons when reprogrammed with regulatory genes involved in retinal neurogenesis. Depending on the regulatory gene used, reprogramming generates cells exhibiting traits of photoreceptor cells, amacrine cells and/or young ganglion neurons. Take home message: Gene-directed reprogramming of chick RPE can efficiently generate cells that exhibit traits of retinal neurons. Remaining to be addressed is the question of whether the results from chicks apply to mammals. Since the RPE is located adjacent to the neural retina, RPE reprogramming, if successful in mammals, may offer an approach to repopulate the neural retina without involving cell transplantation. © 2010 Informa UK Ltd.