Epithelial-mesenchymal transition (EMT) allows polarized epithelial layers to locally dissolve and create fibroblast-like or myofibroblastic cell derivatives. EMT resembles other processes of transdifferentiation from one differentiated cell type to another and is critical for proper embryonic development. Furthermore, EMT describes similar processes between endothelial and myoepithelial cells occurring during blood vessel remodeling. All such processes are triggered and controlled by the concerted action of multiple extracellular growth/morphogenetic factors, TGF-β being one of them. The mechanism by which TGF-β elicits EMT has been a major topic of current research. This is due to the relevance EMT has to the processes of tumor cell invasiveness and metastasis on the one hand, and to fibrotic conditions on the other. Here we emphasize on mechanisms of signal transduction and specific gene targets of the TGF-β pathway that are critical effectors of EMT.