Methotrexate (MTX) is one of the most useful drugs for the treatment of various rheumatic diseases in children, mainly juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), and localised scleroderma. MTX is considered the standard treatment of JIA, particularly of those subgroups with polyarticular course. JIA response and remission rates to MTX are the standard for comparison with other drug modifying anti-rheumatic drug (DMARD) and biologic agents in clinical trials. On the other hand, short and long-term data suggest that MTX is a safety drug in the paediatric population with rheumatic diseases. Not surprisingly, MTX is the DMARD of choice in JIA either as monotherapeutic drug or in combination with biologic agents.