The article reviews the advancements and challenges in CRISPR-based gene therapies for monogenic blood disorders and muscular dystrophy. CRISPR/Cas9 technology has revolutionized gene therapy by enabling precise genome editing, particularly in hematological and neuromuscular disorders. For blood disorders, such as β-hemoglobinopathies and primary immunodeficiencies, CRISPR/Cas9 has been used to correct genetic mutations, restore fetal hemoglobin production, and correct pathogenic point mutations. The FDA's approval of Casgevy for severe sickle cell disease and transfusion-dependent β-thalassemia marks a significant milestone. In neuromuscular disorders, CRISPR/Cas9 has been instrumental in generating new cellular and animal models of Duchenne muscular dystrophy (DMD), facilitating the development of therapeutic solutions. Various CRISPR-based strategies, including exon deletion, exon skipping, exon reframing, HDR-mediated gene correction, base editing, prime editing, and CRISPR activation, have shown promising results in preclinical studies. However, challenges such as delivery methods, safety, and immunological concerns remain to be addressed. The review highlights the transformative impact of CRISPR/Cas9 on patients with these debilitating conditions and the ongoing efforts to overcome current limitations.The article reviews the advancements and challenges in CRISPR-based gene therapies for monogenic blood disorders and muscular dystrophy. CRISPR/Cas9 technology has revolutionized gene therapy by enabling precise genome editing, particularly in hematological and neuromuscular disorders. For blood disorders, such as β-hemoglobinopathies and primary immunodeficiencies, CRISPR/Cas9 has been used to correct genetic mutations, restore fetal hemoglobin production, and correct pathogenic point mutations. The FDA's approval of Casgevy for severe sickle cell disease and transfusion-dependent β-thalassemia marks a significant milestone. In neuromuscular disorders, CRISPR/Cas9 has been instrumental in generating new cellular and animal models of Duchenne muscular dystrophy (DMD), facilitating the development of therapeutic solutions. Various CRISPR-based strategies, including exon deletion, exon skipping, exon reframing, HDR-mediated gene correction, base editing, prime editing, and CRISPR activation, have shown promising results in preclinical studies. However, challenges such as delivery methods, safety, and immunological concerns remain to be addressed. The review highlights the transformative impact of CRISPR/Cas9 on patients with these debilitating conditions and the ongoing efforts to overcome current limitations.