The myelodysplastic syndromes represent a heterogeneous series of clonal hematologic neoplasms characterized by morphologic dysplasia, aberrant hematopoiesis and a variable risk of progression to acute myeloid leukemia. These syndromes have a complex pathobiology, and ineffective hematopoiesis is a well-recognized feature of all of them. Normal blood cell maturation, differentiation, function, and survival are impaired, and these abnormalities contribute to the development of peripheral blood pancytopenia. The majority of patients succumb to complications of either bone marrow failure or leukemic progression. The fact that the majority of patients are elderly and have other comorbidities complicates therapeutic decision making and necessitates the development of individualized treatment strategies.