Variations in the Crumbs homolog-1 (CRB1) gene lead to autosomal recessive retinal dystrophies such as early-onset retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA). No treatment is yet available for these patients. Adeno-associated virus (AAV) mediated gene therapy for hereditary retinal diseases holds great promise proven by the large number of active clinical trials. We here summarized the knowledge about the localization and function of CRB1 in the retina and the main pathological features resulting from loss of CRB1 function in humans and in rodents. This know-how is being applied to design and develop AAV gene therapy vectors for the treatment of CRB1-Hereditary retinopathies. Knowing which cell types express the CRB proteins, the possible redundancy of function between CRB1 and CRB2, and the AAV tropism in the human retina, will allow us to rationalize about the AAV capsid, promoter and route of administration that should be used in the AAV vector in order to efficiently and specifically deliver CRB1 or CRB2 into the human retina.