Myelodysplastic syndromes (MDS), discussed in this chapter, are a heterogeneous group of clonal hematopoietic disorders that have an increased risk of progression to acute myeloid leukemia (AML). The prognosis of MDS patients varies significantly based on both patient and disease characteristics. Various classifications have been proposed to better prognosticate patient outcomes. The French-American-British (FAB) classification is the oldest scheme for classifying MDS, dividing it into five subtypes. The World Health Organization (WHO) reclassified MDS in 2000 and 2008 based on clinical data, but the system remained predominantly a morphologic classification. Today, the most widely accepted MDS prognostic models are based predominantly on marrow morphology, cytogenetics, and cytopenias. However, prognostic models are only valid in the context of available therapies and thus have limited use, basically just identifying patients with high-risk disease who should proceed to allogeneic hematopoietic stem cell transplantation, if possible. Our knowledge of both somatic mutations and epigenetic abnormalities in this disease is increasing rapidly, and these findings are likely to be incorporated into future prognostic models and may help guide therapeutic options.