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Exosomes are cell-derived, biologically active membrane-bound vesicles, and are emerging as key modulators of hematopoiesis. Recent studies have provided a clearer understanding of the mechanisms whereby blast-derived exosomes act to suppress hematopoiesis in acute myeloid leukemia (AML).Exosomes released from leukemia blasts have been shown to suppress hematopoietic progenitor cell (HPC) functions indirectly through stromal reprogramming of niche-retention factors and also as a consequence of AML exosome-directed microRNA delivery to HPC. Furthermore, exosomes secreted by AML blasts remodel the bone marrow niche into a leukemia growth-permissive microenvironment.Exosomes suppress hematopoiesis in AML. Strategies to block the production, secretion and reprogramming that exosomes induce may be a novel therapeutic approach in AML and other leukemias.