Increasing HLA mismatches are associated with increased risk of rejection and poor kidney allograft survival. With introduction of concept of Eplet matching with HLA matchmaker by Dr. Rene Duquesnoy, there is great expectation of transplant community that it may provide superior immunologic compatibility than HLA antigen matching. Eplets are sets of polymorphic amino acids configuration on HLA molecule that can induce alloimmune response in setting of transplantation if mismatched. Different tools based on concept of B cell epitopes (HLA matchmaker, HLA epiregistry, HLA-EMMA score, 3D Electrostatic mismatch score), and T cell epitopes (PIRCHE II) are available for immune risk assessment. Despite lot of publications on association of eplet mismatch and graft survival, they are not used in allocation prospectively in most of centres around the world. In this review we are discussing a case highlighting how eplets can be used to understand alloantibody response mounted by patient with kidney allograft failure and how eplet analysis can be used to help find better immunologic match for subsequent transplant. Not all eplets are immunogenic. DeNovo Antibodies develop against the mismatched eplets and can cause antibody mediated injury and loss of an allograft. It is important to identify antibody verified eplets and identify the antibodies against mismatched eplets.