Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of myelomonocytic cells endowed with suppressive activity. MDSC expand and acquire suppressive functions in chronic inflammatory conditions, in particular in neoplastic disorders. As exemplified in two reports in this issue of the European Journal of Immunology, progress has been made in defining MDSC-inducing signals, MDSC phenotypic diversity and spectrum of action. These recent results provide a basis to better define the relationship of MDSC with the adaptive immune responses of mononuclear phagocytes and neutrophils and to exploit their function in a therapeutic setting.