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Objectives The aim of the study was to review the concept of epigenetics and its role in the evolution and treatment of blood disorders. Data sources Data were obtained from Medline databases (PubMed, Medscape, Science Direct) and from materials available on the Internet from 2002 to 2014. Study selection The initial search presented 90 articles, of which 30 met the inclusion criteria. The articles studied the role of epigenetics in the pathogenesis and treatment of hematological diseases. Data extraction If the studies did not fulfill the inclusion criteria, they were excluded. Study quality assessment included whether ethical approval had been obtained, eligibility criteria had been specified, appropriate controls had been established, adequate information was available, and assessment measures had been defined. Data synthesis Each study was reviewed independently; the obtained data were translated into the language of the researcher and have been presented in sections throughout the article. Findings In total 30 potentially relevant publications were included: 29 were human studies and one was an animal study. The studies define epigenetics as changes in gene expression without changes in the DNA itself. Epigenetic regulation was achieved by DNA methylation, histone modification, and microRNA interference. Deregulations in epigenetic mechanisms present an important pathway toward the development of hematological disorders. DNA-demethylating and histone-deacetylating agents are the first era of drugs directed at treating epigenetic deregulations with significant success rates. Conclusion Unlike genetics, the reversible nature of epigenetics makes them highly attractive targets for cancer therapies. DNA-demethylating and histone-deacetylating agents are the first drugs directed at treating epigenetic deregulations. Understanding epigenetic mechanisms will be helpful in introducing new lines of treatment.