The disease modifying antirheumatic drug (DMARD) methotrexate (MTX) is widely used and well accepted for the treatment of patients with rheumatoid arthritis (RA). In ankylosing spondylitis (AS), the use of MTX is not recommended for the axial manifestations and may have some efficacy in the peripheral involvement. For this disease there is a lack of clinical trials, and most of the trials did not show efficacy on the axial symptoms of the disease. Furthermore, there is no evidence that MTX increases the effects or prevents the side effects of TNF-blockers if given in combination. In this paper the available data of MTX in AS will be discussed.