Abatacept is a CTLA-4Ig fusion protein that selectively modulates the CD80/CD86:CD28 costimulatory pathway required for full T-cell activation. The FDA has approved it to be used to treat adult rheumatoid arthritis, juvenile idiopathic arthritis, and adult active psoriatic arthritis. Considering the vital pathogenic role of the CTLA-4 pathway in autoimmune diseases, abatacept could efficiently treat other systemic rheumatic diseases. Here we reviewed the published literature to profile the perspectives about the off-label uses of abatacept, especially in those refractory cases with inadequate responses to conventional therapies and biologic agents. Abatacept can be a promising therapeutic option and contribute to reducing hormone dependence and correlated adverse events.