Gene therapy holds significant promise for treating genetic syndromes, with FDA approvals for conditions such as Spinal Muscular Atrophy (SMA), cerebral adrenoleukodystrophy, β-Thalassemia, hemophilia A/B, retinal dystrophy, and Duchenne Muscular Dystrophy. However, the field faces challenges, including immune responses, secondary infections from immune suppressants, and the unknown outcomes of overexpression. Viral delivery systems can cause adverse effects like hepatotoxicity and lethality if not controlled. The article reviews the current state of gene therapy, highlighting the need for cost-benefit analyses and informed decision-making to avoid foreseeable issues. It also discusses the importance of international cooperation and the role of rare disease research in advancing gene therapy. The review covers publications, funding, clinical trials, and approved therapies, emphasizing the need for refined knowledge of nucleotide delivery systems and off-target impacts. Additionally, it addresses biological considerations such as genetic syndromes, cell and promoter specificity, variant location within proteins, gene isoforms, and the risk of overexpression. The article concludes with a discussion on immune response and the challenges of redosing and pre-existing immunity to viral vectors.Gene therapy holds significant promise for treating genetic syndromes, with FDA approvals for conditions such as Spinal Muscular Atrophy (SMA), cerebral adrenoleukodystrophy, β-Thalassemia, hemophilia A/B, retinal dystrophy, and Duchenne Muscular Dystrophy. However, the field faces challenges, including immune responses, secondary infections from immune suppressants, and the unknown outcomes of overexpression. Viral delivery systems can cause adverse effects like hepatotoxicity and lethality if not controlled. The article reviews the current state of gene therapy, highlighting the need for cost-benefit analyses and informed decision-making to avoid foreseeable issues. It also discusses the importance of international cooperation and the role of rare disease research in advancing gene therapy. The review covers publications, funding, clinical trials, and approved therapies, emphasizing the need for refined knowledge of nucleotide delivery systems and off-target impacts. Additionally, it addresses biological considerations such as genetic syndromes, cell and promoter specificity, variant location within proteins, gene isoforms, and the risk of overexpression. The article concludes with a discussion on immune response and the challenges of redosing and pre-existing immunity to viral vectors.