The myeloproliferative neoplasms (MPNs) are a group of acquired clonal disorders where mutations drive proliferative disease resulting in increased blood counts and in some cases end-stage myelofibrosis. Epigenetic changes are the reversible modifications to DNA- and RNA-associated proteins that impact gene activity without changing the DNA sequence. This review summarizes mechanisms of epigenetic changes and the nucleosome. The drivers and epigenetic regulators in MPNs are outlined. In MPNs, distinct patterns of epigenetic dysregulation have been seen in chronic and in advanced phases. Methylation age and histone modification are altered in MPNs and by further treatment. The alterations found in methylation age in MPNs and with treatment are discussed, and the changes in histone modification with Janus kinase (JAK) inhibition are evaluated. Currently available therapeutic areas where the epigenome can be altered are outlined. Thus, we review the current knowledge and understanding of epigenetics in MPN and consider further management options. Understanding the epigenome and its alteration in MPNs and epigenetic changes associated with the progression of disease will lead to advances in therapeutic options.