In kidney transplantation (KT), overcoming donor shortage is particularly challenging in patients with preexisting donor-specific antibodies (DSAs) against human leukocyte antigen (HLA), called HLA-incompatible KT (HLAi KT), carrying the risk of rejection and allograft loss. Thus, it is necessary to accurately evaluate the degree of sensitization before HLAi KT, and undertake appropriate pretreatment strategies. To determine the degree of sensitization, complement-dependent cytotoxicity has been the only method employed; the development of a method using flow cytometry further improved the test sensitivity. However, these tests present disadvantages, including the need for living cells, with a solid-phase assay developed to resolve this problem. Currently, the method using Luminex (Luminex Corp.) is widely used in clinical practice. As this method measures DSAs using single antigen beads, it is possible to classify immunological risks by measuring the type and amount of DSAs. Furthermore, there have been major advances in methods that involve DSA removal before HLAi KT. In the early stages of desensitization, plasmapheresis and intravenous immunoglobulins were the main treatment methods employed; however, the introduction of CD20 monoclonal antibody and proteasome inhibitors further increased the success rate of desensitization. Currently, HLAi KT has been established as an important transplant method, but an understanding of DSAs and a novel desensitization treatment are warranted.