Cyclosporine has been used successfully as a systemic immunomodulator for more than two decades, and numerous studies have investigated its mechanisms of action. In 2003 an ophthalmic formulation, cyclosporine 0.05% ophthalmic emulsion, was approved by the FDA to treat dry eye disease. Topical cyclosporine emulsion has also been investigated for treatment of other ocular surface disorders that may have an immune-based inflammatory component. In these trials, cyclosporine 0.05% ophthalmic emulsion has shown efficacy for management of posterior blepharitis, ocular rosacea, post-LASIK dry eye, contact lens intolerance, atopic keratoconjunctivitis, graft-versus-host disease, and herpetic stromal keratitis. As these disorders are often refractory to other available treatments, ophthalmic cyclosporine is a welcome nontoxic adjunct or replacement to potentially toxic topical or systemic immunosuppressive therapies.