Adeno-associated viral (AAV) vectors have emerged as crucial tools in advancing gene therapy for skeletal diseases, offering sustained expression with low post-infection immunogenicity and pathogenicity. Preclinical studies support the therapeutic efficacy and safety of these vectors, highlighting their potential in treating both rare and prevalent skeletal diseases. Emerging technologies and innovations in AAV-mediated gene therapy, such as gene addition, replacement, silencing, and editing, offer new approaches to clinical application. Recent advancements in AAV vector genome design and capsid engineering have improved transduction efficiency, tissue-specific targeting, and vector safety. Preclinical studies have demonstrated the potential of AAV-mediated gene therapy in treating rare diseases like fibrodysplasia ossificans progressiva (FOP) and osteogenesis imperfecta (OI), as well as prevalent conditions like osteoporosis, bone fractures, critical-sized bone defects, and osteoarthritis. Despite existing limitations, such as high cost and safety concerns, AAV-mediated gene transfer is a promising approach for delivering therapeutic genes to the skeleton, addressing the unmet needs in the treatment of skeletal disorders. This review provides a comprehensive overview of the therapeutic advancements, challenges, limitations, and solutions within AAV-based gene therapy for skeletal diseases.Adeno-associated viral (AAV) vectors have emerged as crucial tools in advancing gene therapy for skeletal diseases, offering sustained expression with low post-infection immunogenicity and pathogenicity. Preclinical studies support the therapeutic efficacy and safety of these vectors, highlighting their potential in treating both rare and prevalent skeletal diseases. Emerging technologies and innovations in AAV-mediated gene therapy, such as gene addition, replacement, silencing, and editing, offer new approaches to clinical application. Recent advancements in AAV vector genome design and capsid engineering have improved transduction efficiency, tissue-specific targeting, and vector safety. Preclinical studies have demonstrated the potential of AAV-mediated gene therapy in treating rare diseases like fibrodysplasia ossificans progressiva (FOP) and osteogenesis imperfecta (OI), as well as prevalent conditions like osteoporosis, bone fractures, critical-sized bone defects, and osteoarthritis. Despite existing limitations, such as high cost and safety concerns, AAV-mediated gene transfer is a promising approach for delivering therapeutic genes to the skeleton, addressing the unmet needs in the treatment of skeletal disorders. This review provides a comprehensive overview of the therapeutic advancements, challenges, limitations, and solutions within AAV-based gene therapy for skeletal diseases.