Making quick promises of major biomedical breakthroughs based on exciting discoveries at the bench is tempting. But the meandering path from fundamental science to life-saving clinical applications can be fraught with many hurdles. Epigenetics, the study of potentially heritable changes of gene function without modification of the underlying DNA sequence, has dominated the biological research field during the last decade and encountered a large public success. Driven by the unfolding of molecular biology and recent technological progress, the term has evolved significantly and shifted from a conceptual framework to a mechanistic understanding. This shift was accompanied by much hype and raised high hopes that epigenetics might hold both the key to deciphering the molecular underpinning of complex, non-Mendelian diseases and offer novel therapeutic approaches for a large panel of pathologies. However, while exciting reports of biological phenomena involving DNA methylation and histone modifications fill up the scientific literature, the realistic clinical applications of epigenetic medicines remain somewhat blurry. Here, we discuss the state of the art and speculate how epigenetics might contribute to prognostic and therapy approaches in the future.