Regulatory T cells (Treg) are a subset of T lymphocytes which are essential to maintain immune tolerance. The abnormal number and function of Treg can lead to autoimmune status and disrupt homeostasis of T cells. It had been well demonstrated that activated T cell nuclear factor (NFAT), B lymphocyte-induced mature protein (BLIMP)-1, interferon regulatory factor (IRF)4 play important roles in regulating the growth and development of T lymphocytes. Those molecules are crucial for development and suppressive function of Treg. This review will summarize the regulatory function and their potential mechanism of NFAT, BLIMP-1 and IRF4 on Treg.