Transforming growth factor (TGF)-β family is a cytokine family with various biological processes and forms a highly homologous group of three mammalian isoforms, TGF-β1, TGF-β2, and TGF-β3. Most of the attention on TGF-β family in immunology has been mainly focused on TGF-β1 in that TGF-β1 induces anti-inflammatory regulatory T cells (Treg), and inflammatory T helper 17 (Th17) cells in combination with interleukin-6. Although little attention has been focused on the immunological roles of TGF-β2 and TGF-β3, the function of TGF-β3 for maintaining immunological homeostasis has recently been identified such as the induction of Th17 cells and direct regulatory effects on humoral immunity. TGF-β1 and TGF-β3 shares similar anti-inflammatory or pro-inflammatory functions, but exhibits significantly different effects on fibrosis and chondrogenesis. For the clinical application of TGF-βs, the mechanisms by which each TGF-β isoform regulates immunity has to be elucidated. In this review, we provide an overview of the effects, cellular targets, and therapeutic potential of TGF-βs on immune responses and autoimmune diseases.