Evidence of a significant pathogenetic role of donor-reactive antibodies (DRA) in kidney allograft rejection is accumulating. At least, partially owing to the recent discovery of the complement split product C4d as a valuable rejection marker, antibody-mediated rejection (AMR) has regained increasing attention. We review here the value of various diagnostic criteria, including immunohistochemistry (C4d staining), histomorphology and posttransplant serology, for the diagnosis of AMR. Furthermore, the mechanisms underlying alloantibody/complement-mediated allograft injury are discussed in detail. Finally, a thorough discussion of recently proposed "anti-humoral" therapeutic strategies is provided.