The US Food and Drug Administration (FDA) has approved etranacogene dezaparvovec (Hemgenix), marking a significant milestone in both hematology and gene therapy. This is the first FDA approval of a gene therapy for hemophilia B and the first approval of a liver-targeted adeno-associated virus (AAV) vector gene therapy. The approval is based on extensive nonclinical studies and clinical trials that demonstrated both short-term safety and phenotypic improvement. The phase 2b and phase 3 trials included 57 participants, showing that 96% of participants could stop factor IX (FIX) prophylaxis, with the study demonstrating noninferiority to FIX prophylaxis in terms of the primary endpoint, annualized bleeding rate. Key secondary endpoints, such as the annualized infusion rate and plasma FIX activity levels, were also significantly improved. The most common adverse reactions included liver enzyme elevation, headache, flu-like symptoms, infusion-related reactions, creatine kinase elevation, malaise, and fatigue, but these were mostly transient. One participant developed hepatocellular carcinoma, but molecular analysis showed no evidence of vector-related insertional mutagenesis. The approval of Hemgenix stands on the shoulders of over 20 years of gene therapy research and holds promise for genomic medicines.The US Food and Drug Administration (FDA) has approved etranacogene dezaparvovec (Hemgenix), marking a significant milestone in both hematology and gene therapy. This is the first FDA approval of a gene therapy for hemophilia B and the first approval of a liver-targeted adeno-associated virus (AAV) vector gene therapy. The approval is based on extensive nonclinical studies and clinical trials that demonstrated both short-term safety and phenotypic improvement. The phase 2b and phase 3 trials included 57 participants, showing that 96% of participants could stop factor IX (FIX) prophylaxis, with the study demonstrating noninferiority to FIX prophylaxis in terms of the primary endpoint, annualized bleeding rate. Key secondary endpoints, such as the annualized infusion rate and plasma FIX activity levels, were also significantly improved. The most common adverse reactions included liver enzyme elevation, headache, flu-like symptoms, infusion-related reactions, creatine kinase elevation, malaise, and fatigue, but these were mostly transient. One participant developed hepatocellular carcinoma, but molecular analysis showed no evidence of vector-related insertional mutagenesis. The approval of Hemgenix stands on the shoulders of over 20 years of gene therapy research and holds promise for genomic medicines.