Given the severe shortage of deceased-donor organs in Japan, the use of living-donor kidney transplantation (LKT) strategies, such as ABO-incompatible living-donor kidney transplantation, has expanded rapidly. ABO-incompatible LKT was initially performed following splenectomy and antibody removal; however, immunosuppressive protocols for ABO-incompatible LKT have changed markedly over recent years in Japan. Mycophenolate mofetil, calcineurin inhibitors and corticosteroids are now used to achieve desensitization before transplantation, and thereby suppress acute antibody-mediated rejection. In addition, many institutions now use anti-CD20 antibody (rituximab) instead of splenectomy, which seems to have markedly reduced the incidence of acute antibody-mediated rejection. ABO-incompatible LKT recipients in Japan typically undergo 2–4 sessions of plasma exchange or double-filtration plasmapheresis before transplantation to remove anti-ABO antibodies. In contrast to many Western countries, antibody removal is not routinely performed after kidney transplantation in Japan. Among 1,012 ABO-incompatible LKTs carried out at 92 Japanese institutions during the period 1989–2006, 1-year, 3-year, 5-year and 10-year patient survival rates were 95%, 93%, 91% and 87%, respectively, and the corresponding graft survival rates were 90%, 86%, 80% and 63%, respectively. These data indicate that the outcomes of ABO-incompatible LKT are comparable to those of ABO-compatible LKT. This Review summarizes Japan's experience with ABO-incompatible LKT.