Methotrexate is a folic acid antagonist and immunosuppressive agent, which is being increasingly used in various ocular inflammatory diseases. Its use in ophthalmology has been increasing in recent years because of its anti–inflammatory activity and corticosteroid–sparing objective. It is currently used in recurrent anterior uveitis, intermediate uveitis, posterior or panuveitis, scleritis, peripheral ulcerative keratitis, necrotizing keratitis in rheumatoid arthritis, high–risk penetrating keratoplasty, etc. In addition to systemic administration of drug, intraocular administration of methotrexate can be a promising treatment option for uveitis. This article reviews the current trends and uses of methotrexate in ophthalmology and its related complications.