Low-dose methotrexate (LD-MTX) is the anchor drug used in the treatment of various rheumatological illnesses. There are a lot of misconceptions associated with the long-term use of MTX in the minds of practitioners. The origin of most of these myths stems from the ill effects associated with high-dose MTX used in cancer chemotherapy. In this review, we have summarised and discussed the latest data regarding the safety of LD-MTX. The current evidence underscores the safety of LD-MTX. It is not associated with liver and lung fibrosis as previously thought. Other major concerns such as bone marrow suppression and increased risk of infection are rare with chronic LD-MTX therapy. Hypersensitivity pneumonitis is a rare acute lung toxicity associated with MTX intake, it does not cause interstitial lung disease and in fact, may be protective against it. There is a slight concern about the increased risk of skin malignancy associated with MTX intake
however, association with no other malignancy has been found. It has taken many decades for researchers to clear the various preconceptions associated with MTX. It is time for the academic community to embrace LD-MTX as a new, separate and reinvented drug.