Since its initial description in 2001, chronic humoral rejection (CHR, aka 'chronic anti-body-mediated rejection') has been recognized as a distinct and common cause of late graft dysfunction and loss. The pathology is focused on the microvascular components of the kidney, manifested by endothelial 'activation', multilamination of glomerular and peritubular capillary basement membranes, interstitial fibrosis and tubular atrophy, and sometimes chronic transplant arteriopathy. Diagnosis requires a biopsy and demonstration of the complement degradation product, C4d in peritubular and/or glomerular capillaries. For definitive diagnosis, detection of donor-specific anti-endothelial antibodies is required (most commonly to class II MHC antigens). Here we review the diagnostic criteria, pathologic manifestations, new molecular markers and related studies in experimental animals.