Epigenetics refers as the appearance of heritable changes in gene expression without any alteration in DNA sequence. Mechanisms such as acetylation and deacetylation of histones, global genome hypomethylation and DNA hypermethylation are involved in transcriptional regulation of tumor suppressor genes and genes involved in apoptosis and cell cycle control in various types of hematological malignancies. The appearance of this type of mechanism is related with disease progression and treatment resistance in patients with chronic myeloid leukemia; therefore, the detection of epigenetic alterations has become an innovative tool in monitoring the tumor. Besides, the use of demethylating agents as epigenetic therapy is an alternative and complementary therapy because its use enhances the clinical response of patients with resistance to tirosine kinase inhibitors.