Kidney transplant recipients may develop de novo anti-HLA and non-HLA antibodies after transplantation. Although these antibodies may be donor-specific or non-donor-specific, their presence may increase the risk for acute and chronic rejection, thereby decreasing allograft survival. The introduction of more sensitive and specific methods to detect anti-HLA antibodies, such as Flow Specific Beads and FlowPRA, both before and after transplantation, will help to define immunologically high-risk kidney transplant recipients. Thus, posttransplantation monitoring of anti-HLA antibody production will allow the identification of kidney transplant recipients who might be at increased risk for late allograft failure. Moreover, knowledge of alloantibody status after transplantation may help to guide the appropriate use of immunomodulatory agents to downregulate anti-HLA antibody production.