Myeloid derived suppressor cells (MDSCs) are defined in mice on the basis of CD11b and Gr-1 marker expression and the functional ability to inhibit T lymphocyte activation. Nevertheless the term ‘heterogeneous’ remains the first, informal feature commonly attributed to this population. It is clear that CD11b⁺Gr-1⁺ cells are part of a myeloid macropopulation, which comprises at least two subsets of polymorphonuclear and monocytic cells with different immunosuppressive properties. While recent literature shows substantial agreement on the immunoregulatory property of the monocytic MDSC subset, there is still contrasting evidence on the role of the granulocytic fraction. Moreover, this dichotomy holds true for human MDSCs. We attempt here to summarize conflicting findings in the field and provide some possible, unifying explanations.