The epithelial-mesenchymal transition (EMT) is a critical process in embryonic development and tissue repair, but also contributes to disease progression, including organ fibrosis and cancer. EMT and endothelial-mesenchymal transition (EndMT) are driven by transcription factors that alter gene expression to promote loss of cell-cell adhesion and shift cells to a mesenchymal phenotype. These processes are regulated by signaling pathways such as TGF-β, BMP, Wnt-β-catenin, Notch, Hedgehog, and receptor tyrosine kinases, which respond to signals from the microenvironment. Understanding these mechanisms can enable therapeutic control of EMT to promote tissue regeneration, treat fibrosis, and prevent cancer metastasis. Key EMT-inducing transcription factors include Snail1, Snail2, Twist, ZEB1, ZEB2, and LEF-1. These factors repress E-cadherin expression and promote mesenchymal markers, leading to changes in cell morphology and function. TGF-β signaling, through SMAD-dependent and -independent pathways, plays a central role in EMT by activating transcription factors and modulating cytoskeletal dynamics. Other signaling pathways, such as those involving RTKs, Wnt, Notch, and Hedgehog, also contribute to EMT by regulating transcription factors and ECM remodeling. Matrix signaling, including integrin interactions with collagen and fibronectin, further influences EMT by modulating cell adhesion and migration. The dynamic interplay between these pathways highlights the complexity of EMT regulation and its role in both normal development and disease.The epithelial-mesenchymal transition (EMT) is a critical process in embryonic development and tissue repair, but also contributes to disease progression, including organ fibrosis and cancer. EMT and endothelial-mesenchymal transition (EndMT) are driven by transcription factors that alter gene expression to promote loss of cell-cell adhesion and shift cells to a mesenchymal phenotype. These processes are regulated by signaling pathways such as TGF-β, BMP, Wnt-β-catenin, Notch, Hedgehog, and receptor tyrosine kinases, which respond to signals from the microenvironment. Understanding these mechanisms can enable therapeutic control of EMT to promote tissue regeneration, treat fibrosis, and prevent cancer metastasis. Key EMT-inducing transcription factors include Snail1, Snail2, Twist, ZEB1, ZEB2, and LEF-1. These factors repress E-cadherin expression and promote mesenchymal markers, leading to changes in cell morphology and function. TGF-β signaling, through SMAD-dependent and -independent pathways, plays a central role in EMT by activating transcription factors and modulating cytoskeletal dynamics. Other signaling pathways, such as those involving RTKs, Wnt, Notch, and Hedgehog, also contribute to EMT by regulating transcription factors and ECM remodeling. Matrix signaling, including integrin interactions with collagen and fibronectin, further influences EMT by modulating cell adhesion and migration. The dynamic interplay between these pathways highlights the complexity of EMT regulation and its role in both normal development and disease.