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In the 1980s, the cloning of factor VIII (FVIII) and FIX genes led to several clinical advances, such as the genotyping of hemophilia patients, the development of recombinant FVIII and FIX molecules for the treatment of hemophilia, and, most recently, gene therapy. Valoctocogene roxaparvovec and etranacogene dezaparvovec are the first gene therapy molecules for the treatment of hemophilia A and B, respectively, to obtain marketing authorization; one authorization was granted in Europe and the other in the United States. Other gene therapy molecules are currently under development, including some based on approaches other than vectorization by adeno-associated virus (AAV), such as gene editing. The molecules soon to hit the French market include a single intravenous injection of an AAV-derived vector designed to deliver FVIII or FIX genes into hepatocytes, in order to induce endogenous synthesis and the secretion of the missing coagulation factor. The recent clinical trials that led to the two marketing authorizations, as well as those assessing other molecules for gene therapy, show clinical efficacy of gene therapy for at least five years after a single administration of an AAV vector, the potential liver toxicity of which requires careful monitoring of patients during the first year of the treatment. An asymptomatic increase in alanine aminotransferase is commonly observed in the first twelve months after gene transfer, and immunosuppressive treatment, most often using corticosteroids, may be necessary. Rapid knowledge development is currently taking place in this fascinating scientific field. The French Reference Center for Hemophilia faces the challenge of implementing national organizational strategies to allow French patients to benefit from this innovative therapy in a safe environment, ensured by a multidisciplinary approach involving many specialists, including hematologists, hepatologists, psychologists, and pharmacists.