Heart failure is one of the main causes of mortality in developed countries and is frequently associated with cardiac hypertrophy. Gene expression reprogramming in cardiac myocytes is a key feature of heart hypertrophy and failure and is characterized by upregulation of fetal genes and decreased expression of some subsets of adult ones. The full picture of signaling events underlying gene transcription in these pathophysiologic states is not completely understood, but recent evidence suggests a major role for epigenetics. This report provides an overview of the mechanisms of epigenetics and how they affect myocardial gene expression during hypertrophy and failure.