Fox-factors modulate epithelial and mesenchymal cell fates in different stages during embryonic development. In the context of cancer they have mainly been described by their impact on cell proliferation, apoptosis and angiogenesis. Several studies have now pointed out that distinct members of the Forkhead transcription factor family are critically involved in modulating epithelial plasticity of carcinoma cells and thereby putatively enhance their metastatic and malignant capacity. Here we highlight these recent findings about new aspects of Fox-factor biology, which suggest that Fox-factors have a central role in the regulation of epithelial cell fates and cancer progression. A comprehensive molecular understanding of Fox-factors in this regard may provide potential new targets for therapeutic intervention.