Heart failure (HF) remains a leading cause of death in patient population with known cardiovascular disease. Within last two decades there are evidences regarding decline to determine newel cases with HF with reduced ejection fraction (HFrEF) in developed countries, whereas the frequency of newly-diagnosed HF with preserved ejection fraction (HFpEF) exhibits dramatically rise. Epigenetic modification is considered a modification of the non- DNA sequences related heritable changes in gene expression of target cells. Epigenetic modifications affect several molecular mechanisms, i.e., DNA methylation and deactylation, ATP-dependent chromatin remodeling, histone modifications, and microRNA regulation. The short commentary is clarified the implication of epigenetic modifications in development of different HF phenotypes.