Tissue fibrosis often presents as the final outcome of chronic disease and is a significant cause of morbidity and mortality worldwide. Fibrosis is driven by continuous expansion of fibroblasts and myofibroblasts. Epithelial-mesenchymal transition (EMT) is a form of cell plasticity in which epithelia acquire mesenchymal phenotypes and is increasingly recognized as an integral aspect of tissue fibrogenesis. In this review, we describe recent insight into the molecular and cellular factors that regulate EMT and its underlying signaling pathways. We also consider how mechanical cues from the microenvironment affect the regulation of EMT. Finally, we discuss the role of EMT in fibrotic diseases and propose approaches for detecting and treating fibrogenesis by targeting EMT.