Myeloid-derived suppressor cells (MDSCs) were initially reported as suppressor of the adaptive immune responses against cancer and other diseases. However, emerging evidence suggest that MDSCs may also support anti-tumor immune responses under certain conditions or may inhibit tumor growth. In the present mini-review, we suggest that such opposing functions of MDSCs are due to phenotypic plasticity of the myeloid cells, allowing them to produce a diverse form of morphology, physiological state, and function in response to environmental conditions. Therefore, they can be manipulated by means of immune modulators to overcome their immune suppressive function.