Heart failure (HF) is a complex syndrome that occurs when the heart is unable to take in and/or eject sufficient blood to meet the needs. HF is generally accompanied by hypertrophic changes of cardiac myocytes, the hallmark of HF. At the molecular level, these changes in cardiomyocyte phenotypes are linked to reprogramming of gene expression. Therefore, understanding the molecular mechanisms involved in these gene expression changes in HF could allow for the development of new therapies for this pathology. One mechanism of gene expression regulation that attracts attention is epigenetic modifications, including DNA methylation, histone methylation and acetylation, microRNA, and long noncoding RNA. In this review, we will discuss diverse functions of these epigenetic modifications in HF, and highlight growing evidence for the important roles of epigenetic changes acting as biomarkers for early diagnosis and prognosis of HF, or even as therapeutic targets in HF.