Recent studies show that alloantibodies mediate a substantial proportion of graft-rejection episodes, contributing to both early and late graft loss. Rejection that is caused by antibody is mediated by different mechanisms from rejection that is caused by T cells, thereby requiring other approaches to treatment and prevention. Antibody induces rejection acutely through the fixation of complement, resulting in tissue injury and coagulation. In addition, complement activation recruits macrophages and neutrophils, causing additional endothelial injury. Antibody and complement also induce gene expression by endothelial cells, which is thought to remodel arteries and basement membranes, leading to fixed and irreversible anatomical lesions that permanently compromise graft function.