Methotrexate is one of the most commonly used drugs in the treatment of rheumatoid arthritis. More than 50 years ago, methotrexate was first used in the field of oncology chemotherapy for the treatment of leukemia. Since then, as the pathogenesis of rheumatoid arthritis was studied in depth, medical doctors gradually discovered in the 1960s that methotrexate could suppress the abnormal immune inflammation in rheumatoid arthritis patients, control the development of the disease, prevent joint deformation and have fewer adverse effects. Since then, methotrexate has been widely used worldwide for the treatment of rheumatoid arthritis and has become the drug of choice in the treatment guidelines for rheumatoid arthritis in various countries, unless there is a contraindication to the use of methotrexate. Methotrexate can be administered orally or by injection for the treatment of rheumatoid arthritis. Methotrexate is used in smaller doses for the treatment of rheumatoid arthritis compared to the treatment of tumors. Therefore, the use of methotrexate in the treatment of rheumatoid arthritis is based on research, and patients can regulate its use under the guidance of rheumatologists.