The article by Christina Scheel and Robert A. Weinberg explores the relationship between epithelial–mesenchymal transition (EMT) and cancer stem cells (CSCs). EMT is a cellular program that enables epithelial cells to acquire mesenchymal properties, facilitating the early steps of metastasis, such as invasion and dissemination. The authors highlight that EMT is orchestrated by a set of transcription factors (TFs) that repress epithelial adhesion and promote mesenchymal traits. These TFs, including Snail, Slug, Zeb1, and Twist, play dual roles in both physical dissemination and the acquisition of the CSC state. The connection between EMT and self-renewal is further supported by molecular links, such as the negative regulation of stemness-related microRNAs by EMT-TFs like Zeb1. Additionally, EMT-TFs can influence apoptosis, contributing to the survival and resistance of CSCs. The dynamic regulation of EMT programs, influenced by contextual signals like TGF-beta and Wnt signaling, is crucial for tumor progression and metastasis. The authors conclude that targeting EMT-TFs or their regulatory pathways may be a promising therapeutic strategy to combat CSCs and overcome therapeutic resistance.The article by Christina Scheel and Robert A. Weinberg explores the relationship between epithelial–mesenchymal transition (EMT) and cancer stem cells (CSCs). EMT is a cellular program that enables epithelial cells to acquire mesenchymal properties, facilitating the early steps of metastasis, such as invasion and dissemination. The authors highlight that EMT is orchestrated by a set of transcription factors (TFs) that repress epithelial adhesion and promote mesenchymal traits. These TFs, including Snail, Slug, Zeb1, and Twist, play dual roles in both physical dissemination and the acquisition of the CSC state. The connection between EMT and self-renewal is further supported by molecular links, such as the negative regulation of stemness-related microRNAs by EMT-TFs like Zeb1. Additionally, EMT-TFs can influence apoptosis, contributing to the survival and resistance of CSCs. The dynamic regulation of EMT programs, influenced by contextual signals like TGF-beta and Wnt signaling, is crucial for tumor progression and metastasis. The authors conclude that targeting EMT-TFs or their regulatory pathways may be a promising therapeutic strategy to combat CSCs and overcome therapeutic resistance.