Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. The pathogenesis of AMD involves dysfunction and loss of the retinal pigment epithelium (RPE), a monolayer of cells that provide nourishment and functional support for the overlying photoreceptors. RPE cells in mammals are not known to divide, renew or regenerate in vivo, and in advanced AMD, RPE loss leads to degeneration of the photoreceptors and impairment of vision. One possible therapeutic approach would be to support and replace the failing RPE cells of affected patients, and indeed moderate success of surgical procedures in which relatively healthy autologous RPE from the peripheral retina of the same eye was transplanted under the retina in the macular area suggested that RPE replacement could be a means to attenuate photoreceptor cell loss. This prompted exploration of the possibility to use pluripotent stem cells (PSCs) as a potential source for “healthy and young” RPE cells for such cell-based therapy of AMD. Various approaches ranging from the use of allogeneic embryonic stem cells to autologous induced pluripotent stem cells are now being tested within early clinical trials. Such PSC-derived RPE cells are either injected into the subretinal space as a suspension, or transplanted as a monolayer patch upon scaffold support. Although most of these approaches are at early clinical stages, safety of the RPE product has been demonstrated by several of these studies. Here, we review the concept of cell-based therapy of AMD and provide an update on current progress in the field of RPE transplantation.