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Increasing national participation in kidney paired donation and implementation of new sharing policies via the current kidney allocation system have brought about greater opportunities for the most highly sensitized patients awaiting a kidney transplant. The purpose of this review is to discuss the application of histocompatibility data in the context of the clinical practice of kidney transplantation as pertains to the sensitized candidate.With desensitization techniques, transplantation across virtually any antibody barrier is technically feasible, but long-term outcomes after transplantation are improved when the immunologic match between donor and recipient is optimized. Solid-phase immunoassays have changed the landscape of histocompatibility testing. These sensitive and specific assays for identifying donor-specific antibody not only help determine feasibility of transplantation but have enabled outcomes studies aimed at understanding the spectrum of risk posed by different antibody profiles. This, in turn, has helped guide decision-making in donor selection, in particular for sensitized patients.Careful evaluation of donor-specific antibody profiles with individualized, patient-specific determination of unacceptable antigens is necessary to ensure that highly sensitized patients receive every opportunity for transplantation.