OBJECTIVE In spite of impressive improvements in short-term outcomes for intestine transplant recipients, late allograft loss continues to plague the field. Attention has mostly been focused on T-cell-mediated cellular mechanisms of allograft rejection to explain these losses; however, as in other forms of solid-organ transplantation, especially kidney and heart, antibody-mediated mechanisms of acute and chronic allograft injury are increasingly being implicated. In this review, the mechanisms of B-cell- and humoral-mediated allograft injury will be briefly discussed along with the limited evidence that exist for invoking antibody-mediated rejection (AMR) as important in intestine transplantation. RESULTS The presence of donor-specific antibody has been reported to increase the incidence and severity of intestine allograft rejection and to worsen the overall prognosis for graft and patient. C4d staining in intestine biopsies is unreliable, and currently it is not possible to diagnose AMR with certainty in intestine transplantation. Treatment of presumed AMR in intestine recipients is purely anecdotal at this time. CONCLUSIONS Further basic and clinical research needs to be conducted to more confidently diagnose and treat AMR in intestinal transplantation.