Cyclosporine is a versatile immunomodulatory drug commonly employed in modern medicine. Although cyclosporine was initially used to prevent solid organ transplant rejection, its indications have extended to treat many inflammatory or autoimmune diseases. Cyclosporin is available for use in oral, intravenous, and topical forms, including eye drops to treat corneal and ocular surface conditions. It is naturally advantageous to administer cyclosporin directly into the eye, avoiding potential and dose limiting systemic adverse effects. However, the transition from systemic to topical administration has been a challenging one. This report reviews the evolution of ophthalmic cyclosporine treatment and explores its clinical impacts and future research directions.