Myeloid differentiation is often disturbed in cancer, leading to reduced frequencies of immunostimulatory dendritic cells and an over-representation of immunosuppressive immature myeloid cells, granulocytes and macrophages. As a result of this skewed myeloid differentiation, a highly immunosuppressive myeloid subset becomes prevalent during cancer development; these myeloid-derived suppressor cells are also recruited as a collateral to certain protumorigenic inflammatory processes, resulting in an effective downregulation of T-cell-mediated immune surveillance and antitumor immunity. In this article, some of the important myeloid cell subsets and mediators involved in cancer-related immune suppression are reviewed. Furthermore, cross-talk between tumors and the myeloid compartment, and ways in which it can suppress effective cell-mediated immunity, are discussed, as well as possible therapeutic approaches to tip the balance in favor of antitumor immunity.