Precision medicine can put clinicians in a position where they must act more as resource allocators than their traditional role as patient advocates. In the allocation of transplantable organs and tissues, the use of eplet matching will enhance precision medicine but, in doing so, generate a tension with the present reliance on rule of rescue and justice-based factors for allocations. Matching donor and recipient human leukocyte antigens (HLA) is shown to benefit virtually all types of solid organ transplants yet, until recently, HLA-matching has not been practical and was shown to contribute to ethnic/racial disparities in organ allocation. Recent advances using eplets from the HLA molecule has renewed the promise of such matching for predicting patient outcomes. The rule of rescue in organ allocation reflects a combination of ethical, policy, and legal imperatives. However, the rule of rescue can impede the allocation strategies adopted by professional medical associations and the optimal use of scarce transplant resources. While eplet-matching seeks to improve outcomes, it may potentially frustrate current ethics-motivated initiatives, established patient-practitioner relationships, and functional conventions in the allocation of medical resources such as organ and tissue transplants. Eplet-matching allocation schemes need to be carefully and collaboratively designed with clear, fair and equitable guidelines that complement functional conventions and maintain public trust.