Myelodysplastic syndromes (MDS) are a diverse group of disorders characterized by disorderly and ineffective hematopoiesis. Patients suffer morbidity from associated cytopenias that result in an increased risk of infection, transfusion-dependent anemia, and bleeding. Despite the variable risk of transformation to acute leukemia, the majority of deaths are due to bone marrow failure. No truly effective treatment exists for MDS, and therapy usually focuses on reducing or preventing complications of the disease. Identification of potential cellular and molecular targets, such as epigenetic modification, has led to novel therapeutic approaches in recent years. An increasing number of diagnostic markers, prognostic parameters, and therapeutic strategies are available and becoming widely accepted.