Histone methylation is one of the important epigenetic regulatory mechanisms, and plays a significant role in a variety of physiological and pathological processes. Many recent studies have shown that abnormalities of histone methylation are closely related with the initiation and progression of myeloid malignancies. The reversibility of histone methylation provides a broad prospect for the discovery and application of specific small molecule drugs. This review summarizes the recent progresses in this area and mainly focuses on the correlation of histone methylation with myeloid malignancies.