Collectively, neurodegenerative diseases impose an escalating global health burden, representing one of the leading causes of death and disability worldwide. Despite their growing prevalence, diagnosis and treatment remain major challenges, partly due to the absence of specific and reliable biomarkers for early detection, disease monitoring, and prognosis. Epigenetic biomarkers are emerging as promising clinical tools, although their potential in the context of neurodegenerative diseases is not yet fully realised. In this review, we provide an overview of advances in the understanding of DNA modifications and chromatin architecture in neurodegeneration, highlighting translational relevance for biomarker discovery and therapeutic development. Finally, building on insights from other diseases where epigenetic biomarkers are already applied, we discuss the key steps required to enable implementation in neurodegenerative diseases.