FK506, renamed tacrolimus, is an immunosuppressive agent used in organ transplants to prevent allograft rejection and graft-versus-host disease. FK506 binds to an immunophilin, FK506-binding protein-12 (FKBP-12), and the resulting complexes inactivate calcineurin, a pivotal protein enzyme in T cell receptor signaling. FK506 in known to induce immunosuppression due to calcineurin inhibition / interruption of the NF-AT pathway of T lymphocytes, recent studies suggest that it has additional anti-inflammatory properties. For instance, FK506 has shown efficacy in the treatment of refractory rheumatoid arthritis, a chronic inflammatory disease. Apoptosis, a form of programmed cellular suicide, may provide a key function in establishing tissue homeostasis, as well as self-tolerance, through eliminating autoreactive immunocompetent cells. In our study, we have demonstrated that FK506 augments steroid-induced T cell apoptosis. Furthermore, FK506 enhances superantigen-induced T cell apoptosis by downregulation of the survival gene, Bcl-XL. The observed potentially apoptotic of FK506 may act as an anti-inflammatory agent by preventing activation of immune system. FK506 also has an additional effect on the glucocorticoid receptor (GR) and its signal transduction. After entry into the cell, FK506 binds to FKBP-52, one of the FK506-binding proteins associated with the GR complex. When cells are exposed to glucocorticoids, steroids bind to the GR and release it from the complex. Free GRs transmigrate into the nucleus where they may interact with transcriptional factors, such as nuclear factor-kB(NF-kB), an important regulator of inflammatory responses. Through binding to FKBP-52 in the GR complex, FK506 may facilitate the nuclear transmigration of GR, which would augment the anti-inflammatory effect of steroids. This paper presents the antiinflammatory potential of FK506 and therapeutic strategies to prevent inflammation using this agent.