New insights into the mechanisms of allorecognition and the interactions of the TCR with the MHC molecule-peptide complex on antigen presenting cells have focused attention on developing novel biological strategies to modify the alloimmune response. Peptides derived from various regions of MHC class I and II molecules and structure-based peptides have demonstrated immunomodulatory effects both in vitro and in vivo. Their binding sites and mechanisms of action are under active investigation. Trials in human transplant recipients, with an MHC class I peptide have already begun.