The myelodysplastic syndromes (MDS) represent a complex spectrum of clonal hematopoietic stem cell disorders manifested by cytopenias, risk of infection, and variable risk of progression to acute myelogenous leukemia. Several theories of MDS pathogenesis exist, with contributions of genetic, epigenetic, apoptotic, differentiation, and cytokine milieu abnormalities. Immune dysregulation has also been implicated in MDS pathogenesis. In some forms of MDS it is evident that immune dysregulation may be a primary pathophysiologic abnormality, while in others the abnormal immune function may represent only a small part of the pathologic puzzle. We review the current literature regarding natural killer (NK) cell, Tcell, and myeloid derived suppressor cell abnormalities in the spectrum of MDS.