Epithelial-to-mesenchymal transition (EMT) and endothelial-to-mesenchymal transition (EndMT) describe complex changes in progenitor lineage, cell morphology, and gene expression. Stimulated by environmental cues, these cellular transitions are essential for elements of embryonic development and can be pathologically dysregulated in disease states. EMT occurs in biological processes such as gastrulation, cardiogenesis, and fibrosis. EndMT is involved in development and tissue fibrosis, but recent studies have implicated this process in musculoskeletal biology and pathology. Tissue engineering and regenerative medicine typically rely on endogenous progenitors or progenitors expanded ex vivo to repair damaged or impaired tissues or organs. The processes of EMT and EndMT may aid in elucidating new methods for reducing fibrosis and identifying novel plastic progenitor populations for tissue repair. This review will discuss the potential for EMT and EndMT to impact on tissue engineering and regenerative medicine.