On December 8, 2023, the US Food and Drug Administration (FDA) approved two autologous gene therapy products, Lyfgenia and Casgevy, for the treatment of individuals with sickle cell disease (SCD) aged 12 and older with recurrent vaso-occlusive events (VOEs). Lyfgenia, developed by bluebird bio, uses a lentiviral vector to transduce autologous hematopoietic stem cells with an anti-sickling globin gene. Casgevy, developed by Vertex Pharmaceuticals, is the first CRISPR-Cas9-based gene therapy, enhancing fetal hemoglobin production. These approvals are the result of decades of research and clinical trials involving over 50 individuals with SCD. The approval of Lyfgenia was based on a US study that demonstrated high gene expression and symptom improvement. The FDA label includes a warning for the risk of hematologic malignancy, a known risk of autologous transplantation. The discovery of CRISPR-Cas9 technology revolutionized genetic therapy, but safety concerns remain, including off-target effects and the need for long-term monitoring. Both therapies have broad FDA indications, but specific guidance is needed for their use in clinical practice. The community faces challenges in accessing these treatments, particularly in low-income countries, and the high costs of therapy pose significant barriers. Despite these challenges, the approval marks a significant milestone in the advancement of gene therapy for SCD, offering hope for many patients and families.On December 8, 2023, the US Food and Drug Administration (FDA) approved two autologous gene therapy products, Lyfgenia and Casgevy, for the treatment of individuals with sickle cell disease (SCD) aged 12 and older with recurrent vaso-occlusive events (VOEs). Lyfgenia, developed by bluebird bio, uses a lentiviral vector to transduce autologous hematopoietic stem cells with an anti-sickling globin gene. Casgevy, developed by Vertex Pharmaceuticals, is the first CRISPR-Cas9-based gene therapy, enhancing fetal hemoglobin production. These approvals are the result of decades of research and clinical trials involving over 50 individuals with SCD. The approval of Lyfgenia was based on a US study that demonstrated high gene expression and symptom improvement. The FDA label includes a warning for the risk of hematologic malignancy, a known risk of autologous transplantation. The discovery of CRISPR-Cas9 technology revolutionized genetic therapy, but safety concerns remain, including off-target effects and the need for long-term monitoring. Both therapies have broad FDA indications, but specific guidance is needed for their use in clinical practice. The community faces challenges in accessing these treatments, particularly in low-income countries, and the high costs of therapy pose significant barriers. Despite these challenges, the approval marks a significant milestone in the advancement of gene therapy for SCD, offering hope for many patients and families.