Epigenetic modifications of our genome involve DNA methylation, covalent modifications of the histone tails, nucleosome occupancy and turnover and higher-order chromatin folding. These mitotically heritable epigenetic modifications can affect transcription regulation and are increasingly recognised to be causally involved in a broad spectrum of human conditions, ranging from monogenic to multifactorial disorders. While our understanding of these epigenetic disease mechanisms steadily increases, the challenge will be to develop new drugs that specifically deal with the epigenetic lesion.