<p>Paediatric oncogenesis is tightly intertwined with errors in developmental processes involving cell specification and differentiation, which are governed by intricate temporal epigenetic signals. As paediatric cancers are characterised by a low number of somatic mutations, dysregulated chromatin landscapes are believed to be key drivers of oncogenesis. Epigenetic dysregulation is induced by mutations and aberrant expression of histones and epigenetic regulatory genes, to altered DNA methylation patterns and dysregulated noncoding RNA expression. In this review, we discuss epigenetic alterations in paediatric cancer oncogenesis and recurrence, and their potential as diagnostic biomarkers. We also discuss various epigenetic drugs that have entered clinical trials for aggressive paediatric cancers. Targeting paediatric-specific epigenetic vulnerabilities may improve recurrence-free survival in high-risk cancers.</p>