Transforming growth factor-β (TGF-β) functions as an immune suppressor by influencing immune cells' development, differentiation, tolerance induction and homeostasis. In human diseases, TGF-β has been revealed as an essential regulator of both innate and adaptive functions in autoimmune diseases. Furthermore, it plays a significant role in cancer by inhibiting immunosurveillance in the tumor-bearing host. A variety of TGF-β neutralizing anti-cancer therapies have been investigated based on the role of TGF-β in immunosuppression. New studies are focusing on combining TGF-β blockade with tumor vaccinations and immunogene therapies.