Myelodysplastic syndromes (MDSs) and related myeloid neoplasms represent heterogeneous diseases with overall poor outcomes related to lack of efficacious agents. Immunotherapy has revolutionized the treatment paradigm in solid malignancies and select hematologic malignancies with durable remissions in treatment-refractory populations. The initial clinical studies using immunotherapy in MDS are under way, although significant efforts are required in which to better understand their role in this disease. Likely, combinations of therapies will be required to improve outcomes in this patient population. Furthermore, identification of novel targets for antibody or T-cell modulation strategies is a matter of intensive investigation and ideally will provide treatment options in the near future for our patients.