CAR-T cell immunotherapy,which is derived from T cells and employed in various diseases,particularly blood disorders,involves in vitro gene modification and infusion for treatment.Despite the significant therapeutic effects of CAR-T cells,challenges such as side effects,toxicity,CAR-T cell exhaustion,the immunosuppressive tumor microenvironment,and ge-netic alterations exist.The clinical efficacy of CAR-T cells in solid tumor treatment is limited,often leading to patient re-lapse.Addressing CAR-T-cell exhaustion remains a significant challenge.Scientists are employing diverse technical approaches to prevent CAR-T-cell exhaustion to increase the reliability and utility of CAR-T-cell therapy.This article delves into the mech-anisms of T-cell depletion and CAR-T-cell exhaustion,along with strategies to alleviate or disrupt CAR-T-cell exhaustion.This review of research progress on CAR-T-cell exhaustion aims to identify optimal strategies for reversing CAR-T-cell function and provide a comprehensive theoretical foundation for enhancing CAR-T-cell therapy technology.