Regulatory T cells (Tregs) play a crucial role in the maintenance of immune homeostasis. The two best studied types of CD4(+) regulatory T cells are the Foxp3(+) Tregs and the T regulatory type 1 (Tr1) cells. CD4(+) regulatory T cells play a protective role in autoimmune disease. On the other hand, they also may have pathogenic properties in infectious diseases and carcinogenesis. Because of their potential for the therapy of various human diseases, factors responsible for expanding regulatory T cells are of interest. One of these factors, the TGFbeta family member activin A, is expressed in different inflammatory conditions, such as inflammatory bowel disease, rheumatoid arthritis, and asthma. Although activin A might have pro- and anti-inflammatory properties depending on the context of expression, this review focuses on the role of activin A for the expansion of the CD4(+) regulatory T-cell pool.