The choice between Janus kinase inhibitors (JAKi) and biologic drugs in rheumatoid arthritis remains a frequent question after failure of conventional therapy. Efficacy of these treatment classes appears similar in both randomized trials and real-world studies. The ORAL Surveillance study raised concerns regarding cardiovascular and oncological risks associated with JAKis in high-risk patients. However, data from international registries do not indicate an increased cardiovascular risk in real-word practice. Oncological data remains more heterogeneous. Treatment decisions should therefore be individualized, taking into account the patient's risk profile, preferences, and the risks associated with persistently uncontrolled inflammatory disease.