MDSCs can be targeted in one of three broadly defined ways. First, they can be directly killed. Low-dose gemcitabine, 5-fluorouracil, and TRAIL receptor ligation have shown efficacy in doing so, both clinically and preclinically. The second category of therapeutic is functional inhibition of MDSC-suppressive machinery. PDE-5 inhibitors, such as taldalafil, as well as NO-releasing aspirin and synthetic triterpenoids act effectively in this manner, in part by reducing the expression of ROS, reactive nitrogen species, and arginase, all central to the ability of MDSCs to inhibit immune responses. Finally, myelopoeisis can be skewed such that MDSC accumulation is inhibited and/or MDSCs are forcefully differentiated into more terminally differentiated, immunostimulatory myeloid cells such as DCs and macrophages. Sunitinib and ATRA have shown efficacy in these two functions, respectively.