Background: Methotrexate (MTX) is the first-line drug in the treatment of rheumatoid arthritis (RA) and the most commonly prescribed disease modifying anti-rheumatic drug. Moreover, it is also used as an adjuvant drug in patients under biologic therapies, enhancing the efficacy of biologic agents. Objectives: To review the literature and update the Portuguese recommendations for the use of MTX in rheumatic diseases first published in 2009. Methods: The first Portuguese guidelines for the use of MTX in rheumatic diseases were published in 2009 and were integrated in the multinational 3E Initiative (Evidence Expertise Exchange) project. The Portuguese rheumatologists based on literature evidence and consensus opinion formulated 13 recommendations. At a national meeting, the recommendations included in this document were further discussed and updated. The document resulting from this meeting circulated to all Portuguese rheumatologists, who anonymously voted online on the level of agreement with the updated recommendations. Results: Results presented in this article are mainly in accordance with previous guidelines, with some new information regarding hepatitis B infection during MTX treatment, pulmonary toxicity monitoring, hepatotoxicity management, association with hematologic neoplasms, combination therapy and tuberculosis screening during treatment. Conclusion: The present recommendations combine scientific evidence with expert opinion and attained desirable agreement among Portuguese rheumatologists. The regular update of these recommendations is essential in order to keep them a valid and useful tool in daily practice.