To increase transplantation access, particularly in living-donor renal transplantation, efforts have been made to overcome the barrier of ABO incompatibility. In adults, the most successful cases have involved renal transplantation. Although the overall goal of reducing antibodies against donor ABO before and after transplantation is a general principle, the protocols used to accomplish this goal vary. More well-designed, controlled clinical trials are needed to establish optimal peritransplantation management protocols. Incompatible liver transplantation still is viewed as a temporary measure until ABO-compatible transplantation can be performed. ABO-incompatible heart and lung transplantation in adults still is not performed intentionally. In children, particularly those with relatively immature immune systems, ABO-incompatible transplantation generally has more success. The immunologic mechanisms leading to successful transplantation are being elucidated. Accommodation is a process whereby the donor organ may participate in its own survival through a series of protective gene responses, possibly in response to low-level incompatible antibody (HLA and ABO). In infants, spontaneous, acquired B-cell tolerance seems to be a primary mechanism. Peritransplantation therapy might be tailored to invoke specific immune graft-sparing mechanisms. The stage is set to eliminate ABO as a barrier to solid-organ transplantation.