In recent years, recurrent somatic mutations in genes encoding proteins involved in DNA methylation and demethylation, and in histone modifications have been reported in myeloid malignancies. Large clinical correlative studies are beginning to clear the clinical importance, prevalence, and potential prognostic significance of these epigenetics modifying gene mutations. Additionally, recent studies shedding light on the role of epigenetics in the pathogenesis of myeloid malignancies has prompted increased interest in development of novel therapies which target DNA and histone posttranslational modifications. In this review, we summarize the current understanding of the epigenetics modifying gene mutation, discuss how contribute to its pathogenesis and clinical feature in AML.