A major biomedical advance from recent years was the finding that gene expression and phenotypic traits may be shaped by potentially reversible and heritable modifications that occur without altering the sequence of the nucleotides, and became known as epigenetic changes. The term ‘epigenetics’ dates back to the 1940s, when it was first used in context of cellular differentiation decisions that are made during development. Since then, our understanding of epigenetic modifications that govern development and disease expanded considerably. The contribution of epigenetic changes to shaping phenotypes brings at least two major clinically relevant benefits. One of these, stemming from the reversibility of epigenetic changes, involves the possibility to therapeutically revert epigenetic marks to re-establish prior gene expression patterns. The strength and the potential of this strategy are illustrated by the first four epigenetic drugs that were approved in recent years and by the additional candidates that are at various stages in preclinical studies and clinical trials. The second particularity is the finding that epigenetic changes precede the appearance of histopathological modifications. This has the potential to facilitate the emergence of epigenetic biomarkers, some of which already entered the clinical arena, catalysing a major shift in prophylactic and therapeutic strategies, and promising to fill a decades-old gap in preventive medicine.