Graft rejection is a serious complication after intestinal and multivisceral transplantation. Classic anti-rejection strategies often focus on addressing the cellular component, however mounting evidence suggests that antibody mediated rejection may also play an important role in patient and graft survival. Bortezomib, a proteasome inhibitor used in the treatment of multiple myeloma, has been found to be useful in treating antibody mediated rejection in kidney transplant recipients. The following case illustrates how bortezomib was used to successfully reverse refractory rejection in a patient following multivisceral transplantation. While the rejection was able to be controlled, this patient's course was complicated by an aggressive viral infection after bortezomib therapy. Bortezomib may be a useful agent in the treatment of rejection after intestinal and multivisceral transplantation; however more data is needed to assess its impact on infectious complications in this complex group of patients.