The article reviews the therapeutic strategy of targeting Janus kinases (JAKs) in immune and inflammatory diseases. JAKs are essential signaling mediators downstream of many pro-inflammatory cytokines, and small-molecule drugs that inhibit JAKs have shown promise in treating conditions like rheumatoid arthritis, psoriasis, and inflammatory bowel disease. The review discusses the biology of JAK inhibitors, focusing on recent clinical trial data, novel agent development, and their use in various immune and inflammatory diseases. It highlights the advantages and limitations of improved JAK selectivity, optimal dosing regimens, and patient selection criteria. The article also explores the safety profile of JAK inhibitors, including concerns about increased infection risk, hematological side effects, and potential impacts on cardiovascular health. Finally, it outlines the development of next-generation JAK inhibitors, including JAK1, JAK3, and TYK2-selective inhibitors, and their potential applications in treating a range of autoimmune and inflammatory disorders.The article reviews the therapeutic strategy of targeting Janus kinases (JAKs) in immune and inflammatory diseases. JAKs are essential signaling mediators downstream of many pro-inflammatory cytokines, and small-molecule drugs that inhibit JAKs have shown promise in treating conditions like rheumatoid arthritis, psoriasis, and inflammatory bowel disease. The review discusses the biology of JAK inhibitors, focusing on recent clinical trial data, novel agent development, and their use in various immune and inflammatory diseases. It highlights the advantages and limitations of improved JAK selectivity, optimal dosing regimens, and patient selection criteria. The article also explores the safety profile of JAK inhibitors, including concerns about increased infection risk, hematological side effects, and potential impacts on cardiovascular health. Finally, it outlines the development of next-generation JAK inhibitors, including JAK1, JAK3, and TYK2-selective inhibitors, and their potential applications in treating a range of autoimmune and inflammatory disorders.