Purpose of Review <p>Janus kinase inhibitors (JAKi) have emerged as an effective oral therapy with a rapid onset of action for moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD). Targeting the JAK-STAT pathway, therapies such as tofacitinib (pan-JAK inhibitor), and selective JAK1 inhibitors like upadacitinib and filgotinib, demonstrate benefit in treating active inflammation and extraintestinal manifestations of inflammatory bowel disease (IBD). However, safety concerns, including risks of infection, herpes zoster reactivation, lipid abnormalities, major adverse cardiovascular events (MACE), venous thromboembolism (VTE), malignancy, and gastrointestinal perforations, have led to increased regulatory scrutiny.</p> Recent Findings <p>Despite these concerns, JAKi can be safely and effectively incorporated into IBD treatment algorithms, with individualized risk evaluation and close monitoring. These risks appear dose-dependent and are more pronounced in high-risk populations, such as older adults or those with pre-existing cardiovascular risk. Preventive strategies, including vaccinations, cardiovascular screening, TB testing, and regular lab monitoring, are essential. JAKi are contraindicated during pregnancy and breastfeeding due to limited safety data.</p> Summary <p>This review highlights the evolving safety profile of JAKi and provides recommendations to optimize their use in clinical practice.&#xa0;</p>