Although current therapies for pretransplant desensitization and antibody mediated rejection (AMR) have had some success, they do not specifically deplete plasma cells that produce antibodies to HLA. Bortezomib, a proteasome inhibitor, has been shown to induce plasma cell apoptosis and has been used in the treatment of AMR; however, there are no reported experiences in using this agent in pretransplant desensitization. We report using bortezomib in conjunction with Rituximab to desensitize a kidney transplant recipient on the waiting list. The patient's anti-HLA antibody titers (calculated PRA- (cPRA)) decreased from 57% to 31% prior to transplantation and the overall strength of his anti-HLA antibodies also decreased. He received a deceased-donor kidney to which he had a single low-level donor specific antibody that was undetectable post transplant. This case report demonstrates the potential safety of bortezomib therapy in treatment of highly sensitized patients awaiting kidney transplant and its association with decreased anti-HLA antibody levels.