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This review will focus on epigenetic modifications utilizing the DNA methylation mechanism, which is potentially involved in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). The putative pathways of HFpEF will be discussed, specifically myocardial fibrosis, myocardial inflammation, sarcoplasmic reticulum Ca²⁺-ATPase, oxidative–nitrosative stress, mitochondrial and metabolic defects, as well as obesity. The relationship of HFpEF to aging and atrial fibrillation will be examined from the perspective of DNA methylation.