Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with suppressive properties that preferentially expand in cancer. Myeloid-derived suppressor cells mainly suppress T-cell proliferation and cytotoxicity, inhibit natural killer cell activation, and induce the differentiation and expansion of regulatory T cells. The wide spectrum of MDSC suppressive activity in cancer and its role in tumor progression have rendered these cells a promising target for effective cancer immunotherapy. In this review we briefly discuss the origin of MDSCs and their main mechanisms of suppression and focus more on the approaches developed up to date targeting of MDSCs in tumor-bearing animals and cancer patients.