Methotrexate (MTX) is a folate analog with anti-proliferative, anti-inflammatory and immunomodulatory effects.It is widely used in clinical practice to treat various diseases, including malignant tumors and autoimmune diseases.MTX is used for treating eye diseases by local injection or whole-body administration. Its safety and efficacy have been confirmed. The intravitreal injection can reduce the whole-body use of glucocorticoids and immunosuppressive agents, so it is applied in ophthalmology increasingly. The specificity of MTX has been found in its application in special patients, such as men and women in pregnancy preparation period, pregnant women, lactating women, children, adolescents and the elderly. The dosage varies from patient to patient. Common adverse reactions to low-dose MTX include gastrointestinal symptoms, liver dysfunction, etc. Serious adverse reactions are relatively rare, but pharmaceutical monitoring is still necessarily needed. This review summaries the usage and adverse reactions of MTX in clinical practice, to provide reference for its application in clinical practice in ophthalmology.