Muller glia originate from neuroepithelium and are the principal glial cells in the retina. During retinal development, Muller glia are one of the last cell types to be born. In lower vertebrates, such as zebrafish, Muller glia possess a remarkable capacity for retinal regeneration following various forms of injury through a reprogramming process in which endogenous Muller glia proliferate and differentiate into all types of retinal cells. In mammals, Muller glia become reactive in response to damage to protect or to further impair retinal function. Although mammalian Muller glia have regenerative potential, it is limited as far as repairing damaged retina. Lessons learned from zebrafish will help reveal the critical mechanisms involved in Muller glia reprogramming. Progress has been made in triggering Muller glia to reprogram and generate functional neurons to restore vision in mammals indicating that Muller glia reprogramming may be a promising therapeutic strategy for human retinal diseases. This review comprehensively summarizes the mechanisms related to retinal regeneration in model animals and the critical advanced progress made in Muller glia reprogramming in mammals.