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It is often difficult to distinguish myelodysplastic syndrome (MDS) from severe aplastic anemia (SAA) because both can present with profoundly hypocellular bone marrows. The distinction matters because although both conditions are complicated by pancytopenia, the risk of progression to acute leukemia is much greater in MDS. This chapter reexamines the relationship between SAA and MDS. The clinical and morphological features and pathophysiology of AA (including moderate and severe forms of acquired AA) are compared with MDS and hypoplastic MDS, with particular reference to new observations implicating autoimmune processes in both conditions. SAA and hypoplastic MDS (HMDS) are discussed in the light of these findings and attempts to separate nonevolving bone marrow failure syndromes from marrow failure progressing to acute leukemia are reviewed. The weight of evidence supports a …