The retina has been at the forefront of translational gene therapy. Proof-of-concept that gene therapy could restore vision in a large animal led to the initiation of the first successful clinical trials and, in turn, to the recent approval of the first gene therapy product for an ocular disease. As dozens of clinical trials of retinal gene therapy have begun, new challenges are identified, which include delivery of large genes, counteracting gain-of-function mutations, and safe and effective gene transfer to diseased retinas. Advancements in vector design, improvements of delivery routes, and selection of optimal timing for intervention will contribute to extend the initial success of retinal gene therapy to an increasing number of inherited blinding conditions. The first FDA-approved gene therapy product for an inherited disease is an adeno-associated virus (AAV)-based vector for a form of blindness. Clinical development of gene therapy for dozens of rare and common retinal diseases is ongoing, although improvements will be required to broaden the success of retinal gene therapy to a growing number of conditions. Transduction of the retina from the vitreous and delivery of genes larger than 5kb are long-standing goals of the field, for which promising results have been recently obtained in animal models. The recent evolution of designer nucleases, including CRISPR/Cas9, allows to edit toxic gain-of-function mutations even in terminally differentiated neurons. Therapeutic approaches which are independent of the underlying mutations are being developed that are based on delivery of either neurotrophic factors to slow down retinal degeneration or optogenetic molecules to sensitize neurons to light.