Abstract: Janus kinase (JAK) is a non-receptor tyrosine kinase, and the JAK-signal transducer and activator of transcription (STAT) signaling pathway can affect cell proliferation, differentiation, apoptosis, and immunomodulation. Since the first JAK inhibitor was approved for marketing, small molecule JAK inhibitors have been a hotspot in global drug research and development. The first-generation JAK inhibitors are non-selective inhibitors. Although they have achieved good therapeutic effects, they generally show severe toxic side effects in clinical setting due to low selectivity. The second-generation JAK inhibitors are selective inhibitors. They can more accurately regulate the signal transduction of cytokines in the JAK-STAT pathway, thus effectively solving the safety problems of the first-generation JAK inhibitors. This article has reviewed the structure of JAK, the action mechanisms of the JAK-STAT pathway, and the research progress of marketed JAK inhibitors and those in phase III clinical trials, aiming to provide references for the research and development of JAK inhibitors.