CD4⁺CD25⁺ T cells are regulatory T cells (CD4⁺CD25⁺ Tregs), which can strengthen immune tolerance. They play a critical role in controlling the development of autoimmune diseases in animals and humans. Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects the peripheral joints and eventually leads to joint destruction. Although the pathogenesis of RA remains unknown, it is supposed to be affected by autoreactive T cells and antibodies. At the same time, to make the CD4⁺CD25⁺ T cells active and to increase the number of the cells are responsible in the therapy of RA in recent studies. Now, many techniques about expansion of Tregs in vitro have been established to overcome the problem of their limited numbers in vivo. It is important to carry out a study of induction or amplification of Tregs in vitro. Here, we review our current understanding of CD4⁺CD25⁺ T cells in RA and the targeting of these cells in RA therapy.