Immune rejection of organ transplants has life-threatening implications. It is believed that allograft rejection is initiated by the activation of lymphocytes following recognition of donor antigens, leading to generation of effector T lymphocytes, alloantibody production, and graft infiltration by alloreactive cells. There is solid evidence that miRNAs are integral for maintaining immune homeostasis and self-tolerance. A deeper understanding of the regulation of the immune response by miRNAs could define new mechanisms for manipulating graft immunity and preventing rejection. The miRNA miR-155 is of particular interest due to its known roles in regulating the expression of genes relevant to allograft rejection and the induction of immune tolerance. Indeed, miR-155 has been shown to dramatically impact both innate and adaptive immune processes, including inflammation, antigen presentation, T-cell differentiation, cytokine production, and T regulatory cell (Treg) functions. The suppressor of cytokine signaling 1 (SOCS1) is a critical regulator of immune cell function and an evolutionarily conserved target of miR-155 in breast cancer cells. We propose that suppression of miR-155 could enhance SOCS1 expression in immune cells and suppress allograft rejection. Further studies on the specific role of miR-155 in allograft rejection may lead to the identification of new targets for therapeutic intervention. Copyright © 2011 Elsevier Ltd. All rights reserved.