In the era of modern immunosuppression, rates of acute rejection have significantly decreased thereby improving short-term outcomes but with only modest improvement in long-term graft survival. We, and others, have demonstrated that de novo HLA donor specific antibody (DSA), which correlates with chronic antibody-mediated rejection (cAMR), is the primary cause of late graft loss. The target of the inflammation and injury related to DSA is the microvascular endothelium, and the principle mediators are complement and NK/Macrophage activation. At present, cAMR is diagnosed after the onset of non-specific graft dysfunction (rising creatinine or new onset proteinuria) in which a biopsy confirms microvascular inflammation in association with a DSA documented in the sera. We reported that de novo DSA is detectable in the serum prior to the onset of cAMR-mediated dysfunction (mean 20 months). Therefore the utility of post-transplant DSA monitoring will be reviewed.