Myelodysplastic syndromes (MDS) are often associated with autoimmune processes that contribute to the cytopenias that characterize this disease group. Ten years ago, several investigators described improvement in the cytopenia of MDS following immunosuppressive treatments (IST) with antithymocyte globulin or cyclosporine. These findings have since been widely confirmed. The consensus is that about 30% of unselected transfusion-dependent patients with MDS given IST have sustained hematologic responses and can regain transfusion independence. Over the past decade, prognostic features have been defined that accurately identify the subset of patients most likely to benefit from IST. With increasing knowledge about the pathophysiology of myelosuppression in MDS, we are beginning to define the immunosuppressive agents and schedules with the greatest chance of causing hematologic improvement. Significantly, long-term follow-up indicates that IST responders have a better progression-free survival than comparable patients with MDS who do not receive IST.