This review is focused on the structure, function, and inhibition of interaction of ICAM-1 and LFA-1. ICAM-1 and LFA-1 are cell adhesion molecules that are involved in the activation of the immune response cells. The reaction of T-cells on “self” antigens is one of the causes of autoimmune diseases, including rheumatoid arthritis, insulin-dependent diabetes mellitus, and multiple sclerosis. Similarly, rejection of organ transplantation results from T-cell attack. In these situations, elimination of the T-cells specific for only the relevant antigens could result in tolerance to the antigen and an alleviation of the disease state. Inhibition of the cell adhesion signal provided by interactions between LFA-1 and ICAM-1 induces the antigen-specific T-cells to die by apoptosis or enter a state of cellular anergy, thereby suppressing the immune response. Therefore, much progress has been achieved in administration of antibodies to ICAM-1 and LFA-1 to suppress immune response in vitro and in vivo. These antibodies have been used to induce immunotolerence in skin, cardiac, kidney, and hepatic allografts. Peptides derived from ICAM-1 and LFA-1 sequences have also been shown to inhibit homotypic and heterotypic T-cell adhesion mediated by ICAM-1/LFA-1 interactions. These peptides presumably inhibit ICAM-1-LFA-1 interactions by binding to their respective counter receptors (ICAM-1 or LFA-1). Therefore, future immnosuppressive drugs may be derived from the inhibitors of ICAM-1/LFA-1 interactions.