Epigenetics, the study of heritable changes in gene expression not involving changes in DNA sequence, plays a key role in the pathogenesis of cancers like myelodysplastic syndrome (MDS) and leukemias. This chapter discusses the role of epigenetics in the pathogenesis of MDS and leukemias. The study of epigenetics has impacted pharmacology leading to the development of a new class of drugs, epigenetic drugs, which attempt to reverse epigenetic changes in clinical disorders. At present, most work is being done on two categories of epigenetic drugs : DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi). The chapter discusses the use of epigenetic drugs in the treatment of MDS and leukemias.