JAK-3, a member of the Janus kinase family, is a protein tyrosine kinase, which plays an important role in the JAK-STAT signaling pathway. Previous studies showed that regulation of JAK-3’s activity plays a crucial role in the treatment of diseases such as rheumatoid arthritis. Many reports have been published with a focus on selective JAK-3 inhibitors, some of which showed excellent JAK-3 selectivity and inhibitory activities. Among the JAK-3 inhibitors reported, tofacitinib has satisfactory therapeutic benefits in the clinical trials, and has been approved for treatment of patients with rheumatoid arthritis. However, some JAK-3 inhibitors exhibited moderate to severe side effects, which need to be controlled by drug improvement. In order to pave the way for improvement of current JAK-3 inhibitors and development of new JAK-3 inhibitors, we provide an outline of the structure of JAK-3 and strategies in development of its inhibitors.