Several desensitization strategies have been investigated for the reversal of acute antibody-mediated rejection or for the removal of preformed anti-HLA antibodies, with the aim to promote access to renal transplantation. Today, their success appears limited or incomplete. Bortezomib, a selective inhibitor of the 26S proteasome, which is largely used in the treatment of multiple myeloma, could be a novel promising desensitizing agent. Its mechanism of action and preliminary clinical use in renal transplantation is reviewed here.