Abstract: Human leukocyte antigen (HLA) sensitization has been previously considered as a contraindication for kidney transplantation. In the past 30 years, with the development of desensitization therapy strategies and immunosuppressants, more and more highly sensitized patients have been eligible for kidney transplantation. However, highly sensitized patients still face a high incidence of hyperacute rejection and antibody-mediated rejection following kidney transplantation, which restricts the success of kidney transplantation and long-term graft survival. At present, exploring effective desensitization regimen is a hot spot in the research of organ transplantation. In this article, the current desensitization therapy strategies, new preparations for desensitization therapy, and the benefits and risks of desensitization therapy were reviewed, and the current status and future direction of desensitization therapies were investigated, aiming to provide reference for resolving the immune barrier, improving the success rate of kidney transplantation and enhancing the quality of life of highly sensitized recipients.