This chapter considers the importance of recipient sensitization with particular reference to renal transplantation. It considers the clinical relevance of both human leukocyte antigen (HLA) and non-HLA antibodies in graft outcomes. Measurement of panel-reactive antibodies (PRA) by complement-dependent cytotoxicity cross-match (CDC) has been largely replaced by more sensitive and less cumbersome solid-phase assays, which report a calculated PRA or population-reactive antibodies. Factors relating to donor, recipient, and locally available resources play a role in the final decision regarding what constitutes an acceptable level of risk and how it is managed. Virtual cross-match has applications in pretransplant risk assessment and can assist with the process of organ allocation. The accuracy of immunological risk assessment has improved the options available for the successful transplantation of highly sensitized recipients has increased. The options include paired-donation programs, acceptable mismatch programs, and desensitization. In HLAi transplants, donor-specific antibody (DSA) levels are monitored using solid-phase assays.