Hematologic malignancies are characterized by a pronounced heterogeneity of tumor clone accounted for by both gene abnormalities and epigenetic changes including abnormal DNA methylation as well as impaired regulation of histone modifications and non-coding RNAs. Recent developments in high-throughput sequencing technology confirmed the key role of epigenetic modifications in the regulation of dynamic biological processes. Over the past years, a considerable body of knowledge has been generated to document the effect of changing epigenetic mechanisms on the development and further progression of hematologic tumors. The analysis of methylation profile leads to detecting the unique epigenetic signatures correlating with clinical outcomes and refractoriness to chemotherapy. This review systematizes current views on the role of DNA methylation in oncohematology and various methods of its analysis as well as the outlook for the therapy targeting the epigenetic abnormalities.