Over the past decade, our understanding of bone marrow failure has advanced considerably. Marrow failure encompasses multiple overlapping diseases, and there is increasing availability of diagnostic tools to distinguish among the subtypes. Identification of genetic alterations that underlie marrow failure has also greatly expanded, especially for myelodysplastic syndromes. Molecular markers are increasingly used to guide the management of myelodysplasia and may distinguish this diagnosis from other marrow failure disorders. This review summarizes the current state of distinguishing among causes of marrow failure and discusses the potential uses of multiple diagnostic and prognostic indicators in the management of myelodysplastic syndromes and other bone marrow failure disorders.