JAK inhibitors are pivotal in treating immune-mediated inflammatory diseases (IMIDs) like rheumatoid arthritis (RA) and inflammatory bowel disease. However, emerging safety concerns warrant careful evaluation. A recent analysis of the FDA Adverse Event Reporting System (FAERS) revealed that RA patients using JAK inhibitors face nearly double the risk of gastrointestinal perforations (GIPs) compared to those on biologics, particularly with concurrent steroid or NSAID use. Additionally, the FDA's ORAL Surveillance study linked tofacitinib with higher rates of cancer and cardiovascular events, prompting regulatory restrictions. These findings highlight the importance of balancing JAK inhibitors' therapeutic benefits with potential risks, emphasizing the need for patient-centred risk assessment and vigilant monitoring to optimize outcomes.