Apoptosis is upregulated in early myelodysplastic syndromes (MDS) and may contribute to the peripheral cytopenias commonly observed. Conversely, leukemic progression is associated with abrogation of programmed cell death (PCD). The stage of hematopoietic cell maturation at which defects in PCD arise and the underlying causes of apoptosis dysregulation remain unknown. This paper outlines the apoptotic process in normal hematopoietic cells and summarizes current data regarding the role, potential causes and clinical implications of altered apoptosis in MDS.