Janus kinase (JAK) inhibitors are highly effective rheumatoid arthritis drugs that raise safety concerns by inhibiting multiple cytokine pathways. The article provides an updated review of the major safety aspects of these drugs with an emphasis on their use in rheumatoid arthritis. The risk of herpes zoster in patients with rheumatoid arthritis is 1.5–2 times higher with tofacitinib treatment than the normal risk in this group. Screening for tuberculosis and hepatitis B and C in patients with active infections and weighing the risks versus benefits is necessary before starting treatment. Live vaccines are not recommended during or immediately before treatment. The safety profile regarding perforations of the lower gastrointestinal tract is favorable, with the same or lower incidence compared to other DMARD drugs.[1]