Regulatory T cells (Treg) play pivotal role in the maintenance of immune homeostasis due to their suppressive abilities. It is important to understand the nature of Treg and the mechanisms by which they function. From recent studies, we can conclude that the development and function of Treg cells is strongly dependent on gene expression. Furthermore, a variety of transcription factors have been proposed to either maintain or inhibit their properties. As it was demonstrated a decade ago, Forkhead box P3 transcription factor (FoxP3), a Treg marker, has the ability to keep them on the right immunosuppressive track. Whether the Treg lineage has the ability of being suppressive or not depends on up- or down-regulation of the foxp3 gene. It can be controlled by other factors present inside the cell. Two of them, Helios and SATB1, are considered to be important in proper Treg development. Helios, a member of the Ikaros family, has been shown to up-regulate expression of FoxP3 protein, whereas SATB1 is known to inhibit its expression. In this review, we will discuss the relations between these three factors, and how they affect Treg development and function.