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Pretransplant and posttransplant alloimmune risk assessment needs to evolve towards a precision medicine model already used in other areas of medicine. Although this has not been possible with traditional risk factors available at the time of transplant, new methods of human leukocyte antigen (HLA) molecular mismatch have generated hope that alloimmune risk assessment may be precise enough for personalized treatment strategies.This review describes the various HLA molecular mismatch methods and some of the recent publications for each method. These include studies that have evaluated HLA molecular mismatch in the context of lung, pancreas and kidney transplant as a correlate with short and long-term outcomes. The limitations of traditional alloimmune risk assessment strategies are highlighted in the context of individualized patient care.Recent studies that have evaluated HLA molecular mismatch in the context of immunosuppression minimization are examples of how more precise measurements of alloimmune risk can lead to novel insights that may help personalize immunosuppression protocols.