Regulatory T (Treg) cells play an important role in the maintenance of self-tolerance and are involved in the prevention of autoimmune diseases and reduce/inhibit the progression of chronic inflammatory diseases. Forkhead box P3 (FoxP3) expression in Treg cells is believed to be a critical factor in the maintenance of Treg cells suppressive function. Multiple mechanisms of action of Treg cells have been proposed, including cell contact-dependent and cytokine-dependent mechanisms. However, no clear picture is available to fully elucidate the regulation of FoxP3 gene expression in Treg cells and how FoxP3-expressing Treg cells mediate the immune response in vivo. This review will discuss the research advancements in Treg cell biology including the transcription factors and signaling pathways involved in the expression of FoxP3 gene as well as the advancements in the understanding of the factors involved in the Treg cell-mediated suppressive mechanisms.