The introduction of both complement 4d (C4d) staining in renal allograft biopsies and sensitive methods to detect anti-human leukocyte antigen antibodies, such as single antigen bead flow assays, into tissue-typing techniques have shown the importance of antibody-mediated alloimmune response in kidney transplantation. The use of these sensitive methods, combined with the increased number of transplants in highly sensitized patients with donor-specific antibodies, or patients receiving desensitization protocols, have increased the awareness and thus the incidence of acute antibody-mediated rejection. Chronic rejection also can be mediated through alloantibodies, and the term chronic antibody-mediated rejection recently was proposed. In this review article we summarize the current knowledge of the role of alloantibodies in transplantation, the diagnosis and treatment of acute and chronic antibody-mediated rejection, and their effect on graft function and outcome.