Members of the transforming growth factor-beta (TGF-beta) family have important roles during embryogenesis, as well as in the control of tissue homeostasis in the adult. They exert their cellular effects via binding to serine/threonine kinase receptors. Members of the Smad family of transcription factors are important intracellular messengers, and recent studies have shown that the ubiquitin ligase TRAF6 mediates other specific signals. TGF-beta signaling is tightly controlled by post-translational modifications, which regulate the activity, stability, and subcellular localization of the signaling components. The aim of this review is to summarize some of the recent findings on the mechanism of TGF-beta signaling to growth arrest, apoptosis, and epithelial-mesenchymal transition.