Janus Kinase (JAK) inhibitors are novel targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs). The new class of small molecule drugs represents an important alternative to treat moderate-to-severe rheumatoid arthritis (RA) patients with non-or inadequate-response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biological disease-modifying antirheumatic drugs (bDMARDs). The JAK inhibitors target one or more kinases of the JAK family (JAK1, JAK2, JAK3, and non-receptor tyrosine-protein kinase TYK2) and inhibit multiple pro-inflammatory cytokines, such as interleukin (IL)-6, IL-10, and interferon (IFN)-g.(2,3) Baricitinib (JAK1/JAK2 inhibitor) and tofacitinib (JAK1/JAK3 inhibitor) are the first members of this class approved in the United States (US) and Europe to treat RA (Figure ). While a dose-response effect was observed in the risk of thrombosis in clinical trials of both baricitinib and tofacitinib, there is no clear mechanism associated to the pharmacological target that could explain the risk of thrombosis associated with JAK inhibitors. Thus, the increased risk of these safety concerns is heavily debated.