The epithelial-to-mesenchymal transition (EMT) is a reversible change in cell phenotype that plays a crucial role during normal development and cancer metastasis. EMT imparts embryonic epithelial cells with the ability to migrate and to give rise to organs or tissues at distant sites. During cancer progression, the same developmental process is utilized in an analogous manner to enable cancer cells to move to distant organs and form metastases. The reversion of EMT via the mesenchymal-to-epithelial transition (MET) appears to be required for the formation of secondary tumors at distal sites. The plasticity of epigenomic modifications that control the transcriptional program of cells enables cells to switch back and forth from epithelial and mesenchymal phenotypes during these transitions. Here, we review the interplay between complex epigenomic regulatory mechanisms and various transcription factors involved in EMT leading to changes in gene expression and cell phenotype. We also discuss the way that a deeper understanding of the epigenomic regulation of EMT might shed light onto the process of cancer progression and reveal new targets for novel and more specific anticancer epigenomic therapies.