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Recent studies have significantly improved our understanding of the role microRNAs (miRNAs) play in regulating normal hematopoiesis. miRNAs are critical for maintaining hematopoietic stem cell function and the development of mature progeny.Thus, perhaps it is not surprising that miRNAs serve as oncogenes and tumor suppressors in hematologic malignancies arising from hematopoietic stem and progenitor cells, such as the myeloid disorders. A number of studies have extensively documented thewidespread dysregulation of miRNA expression in human acute myeloid leukemia (AML), inspiring numerous explorations of the functional role of miRNAs in myeloid leukemogenesis. While these investigations have confirmed that a large number of miRNAs exhibit altered expression in AML, only a small fraction has been confirmed as functionalmediators ofAMLdevelopment or maintenance. Herein, we summarize the miRNAs for which strong experimental evidence supports their functional roles in AML pathogenesis. We also discuss the implications of these studies on the development of miRNA-directed therapies in AML