Epigenetic mechanisms have emerged as key targets for therapeutic intervention. However, while a number of organic small-molecular “epidrugs” have been approved for clinical use, no metal-based epigenetic modulator have been successfully approved. Metal complexes exhibit a variety of distinct properties that make them viable alternatives to organic molecules as therapeutic agents. In this review, we highlight recent examples of epigenetic modulation by metal complexes, with a view towards showcasing the different mechanisms exploited by metal complexes for targeting either epigenetic marks or epigenetic pathways for potential therapeutic applications.