Activin is a member of the TGF-beta superfamily and has various effects on diverse biological systems. Activins initiate their cellular responses by binding to their receptors with intrinsic serine/threonine kinase activity and activation of specific downstream intracellular effectors termed Smad proteins. Smads relay the signal from the cell membrane to the nucleus, where they affect the transcription of target genes. Negative regulation of activin signal occurs at the extracellular, membrane, cytoplasmic and nuclear levels. The presence of many mechanisms for regulation shows its importance to normal physiology. Here, we review the latest advances in activin signal transduction.