Tofacitinib is an oral, small molecule JAK inhibitor that targets JAK1/JAK3. Tofacitinib has been approved by the FDA to be used in the treatments of rheumatoid arthritis, psoriatic arthritis, plaque psoriasis and ulcerative colitis. Considering the important pathogenic role of the JAK/STAT pathway in autoimmune disease, tofacitinib could be, theoretically, effective in the treatments of other systemic rheumatic diseases. Here we reviewed the published literature to profile the perspectives about the off-label uses of tofacitinib, especially in those refractory cases with poor response to conventional therapies or biologic agents. Tofacitinib can be a new therapeutic option and help reducing hormone dependence and correlated adverse events.