Tacrolimus is an immunosuppressive drug that has been used widely in organ transplantation and topically for atopic dermatitis. Tacrolimus exerts its immunosuppressive effects by the inhibition of calcineurin, leading to interference with T-cell activation. As T-cell activation plays a major role in the pathogenesis of rheumatoid arthritis, there has been an interest in the use of tacrolimus for the treatment of rheumatoid arthritis. The pharmacological properties of tacrolimus have the potential of suppressing the production of inflammatory cytokines, improvement of joint inflammation, improvement of bone and cartilage destruction, improvement of functional status and relief from arthritic pain. This article reviews the pharmacodynamics, pharmacokinetics, clinical efficacy, safety and role of tacrolimus in the treatment of rheumatoid arthritis.