Janus Kinase inhibitors (JAKis) have been approved for the treatment of Rheumatoid Arthritis (RA) for several years. They are the first oral advanced treatments with efficacy similar to, if not, greater than biologic agents. Recently, concern over their safety was raised by the results from Oral Surveillance trial suggesting that tofacitinib, one of the JAKis was associated with higher cardiovascular adverse events and malignancies than TNF inhibitors. Since then, regulatory authorities have added warnings the labels of JAKis. Should Rheumatologists use JAKis as first line advance treatment has become a controversial topic. Some rheumatologists have argued that biologics should be first line advance treatment since there are extensive effectiveness and safety data. In addition, with the advent of biosimilars, they are the most cost-effective treatment. On the other hand, JAKis are very efficacious and are generally safe apart from older and high-risk patients. When TNF inhibitors are contraindicated and in certain RA patients especially when an oral drug is preferable, JAKis have significant advantage providing patients are involved in the decision-making process.Copyright © 2023. Published by Elsevier B.V.