Epithelial to Mesenchymal Transition (EMT) is a central feature of embryonic development and is also a critical early event in cancer progression and metastasis. Our understanding of the complexity of the chromatin platform and the epigenetic mechanisms that contribute to transcriptional control has expanded dramatically in recent years. These mechanisms include the presence/absence of histone modifications, which form epigenetic signatures that mark active or inactive genes. These signatures are dynamically added or removed by a wide variety of histone-modifying epigenetic enzymes, which more recently have been found to include chromatin-associated signalling kinases. Here, we discuss the multi-layered regulation of gene transcription during EMT in cancer. Given that epigenetics-based therapeutics are showing promise for the treatment of cancer, unravelling the detail of these epigenetic signatures during EMT is crucial to the development of novel therapeutic strategies that exploit these mechanisms.