Gene therapy, which involves inserting corrective genetic material into cells to alleviate disease symptoms, faces significant challenges in practice. Despite the first clinical trials in 1990, numerous obstacles remain, including inefficient delivery systems, lack of sustained expression, and host immune reactions. Over 200 clinical trials are currently underway, but no single success story has emerged. The choice of cell type for gene delivery depends on the nature of the disease, and the amount of therapeutic protein required varies. Gene delivery is the critical bottleneck, with non-viral vectors suffering from poor efficiency and transient expression, while viral vectors face immune responses and the risk of random integration into the host genome. Retroviral vectors, which can infect both dividing and non-dividing cells, have limitations such as inability to infect non-dividing cells and potential oncogene activation. Lentiviral vectors, which can also infect both dividing and non-dividing cells, offer sustained expression but still face immune challenges. Adenoviral vectors, which can cause short-term high-expression, elicit strong immune responses and are limited by pre-existing antibodies. Adeno-associated viral (AAV) vectors, a non-pathogenic single-stranded DNA virus, show promise with sustained expression and low immunogenicity. Clinical trials have shown that existing delivery systems are generally safe, but efficacy depends on efficient gene delivery and sustained expression. Future prospects include advancements in vector design, immunology, and cell biology to create safer and more effective gene delivery systems. Despite challenges, the authors believe that gene therapy will become a routine medical practice in the near future.Gene therapy, which involves inserting corrective genetic material into cells to alleviate disease symptoms, faces significant challenges in practice. Despite the first clinical trials in 1990, numerous obstacles remain, including inefficient delivery systems, lack of sustained expression, and host immune reactions. Over 200 clinical trials are currently underway, but no single success story has emerged. The choice of cell type for gene delivery depends on the nature of the disease, and the amount of therapeutic protein required varies. Gene delivery is the critical bottleneck, with non-viral vectors suffering from poor efficiency and transient expression, while viral vectors face immune responses and the risk of random integration into the host genome. Retroviral vectors, which can infect both dividing and non-dividing cells, have limitations such as inability to infect non-dividing cells and potential oncogene activation. Lentiviral vectors, which can also infect both dividing and non-dividing cells, offer sustained expression but still face immune challenges. Adenoviral vectors, which can cause short-term high-expression, elicit strong immune responses and are limited by pre-existing antibodies. Adeno-associated viral (AAV) vectors, a non-pathogenic single-stranded DNA virus, show promise with sustained expression and low immunogenicity. Clinical trials have shown that existing delivery systems are generally safe, but efficacy depends on efficient gene delivery and sustained expression. Future prospects include advancements in vector design, immunology, and cell biology to create safer and more effective gene delivery systems. Despite challenges, the authors believe that gene therapy will become a routine medical practice in the near future.