Introduction: Inherited retinal dystrophies (IRDs) are the major cause of familial blindness in the Western world, and until recently, have been devoid of pharmacologic treatment options. Biallelic mutations in the RPE65 gene cause a progressive IRD characterized by decreased light sensitivity, constricted visual fields, and impaired visual acuity. Voretigene neparvovec-rzyl (VN), an adeno-associated viral vector gene therapy that delivers a normal copy of the RPE65 gene to retinal pigment epithelium cells lacking a functional version of the gene, was recently approved by the FDA. Areas covered: The VN compound and its mechanism of action are described. Clinical efficacy, durability, and safety of VN from phase 1 follow-on and phase 3 trials of subjects who received the approved dose of 1.5 x 1011 vector genomes are summarized. Expert opinion: The VN phase 3 trial is the first randomized, controlled study completed in gene therapy for a genetic disease. This represents more than a decade of innovative research, including vector design, manufacturing and formulation, surgical delivery procedure, and clinical trial design, as well as the development of a novel end point. In addition to offering a proven therapy for patients with RPE65 mutation–associated IRD, this gene therapy platform is a springboard to developing investigational therapies for other debilitating genetic diseases.