Hematopoietic stem cells (HSCs), characterized as having self-renewal and multi-lineage differentiation potentials, maintain the hematopoietic system through an entire lifespan. Comprehensive understanding of how HSCs are regulated will facilitate the development of new strategies to manage hematopoietic diseases. Past decades of effort unraveled a pivotal role of epigenetic modification via DNA or histone in the regulation of HSC behaviors; however, effects of RNA modification on HSC behaviors have been largely neglected. N6-methyladenosine (m⁶A), as the most prevalent RNA modification in eukaryote, shows versatile functions in various physiological processes. Recent reports demonstrate a critical role of m⁶A mRNA methylation in the determination of HSC fate, including HSC specification during embryogenesis and HSC proliferation and differentiation in adults. Furthermore, dysregulation of m⁶A RNA methylation has been reported to be associated with leukemogenesis. Elucidation of the underlying mechanisms by which m⁶A RNA methylation regulates HSC fate and promotes leukemogenesis may provide an insight for the translation of basic discoveries into clinical practice in treating hematopoietic disorders. Here we review the recent advances in understanding the regulation of m⁶A RNA methylation in hematopoiesis and leukemogenesis.