Metastasis is the direst face of cancer, and it is not a feature solely dependent on cancer cells; however, a complex interaction between cancer cells and host causes this process. Investigating the mechanisms of metastasis can lead to its control. Myeloid-derived suppressor cells (MDSCs) are key components of tumor microenvironment that favor cancer progression. These cells result from altered myelopoiesis in response to the presence of tumor. The most recognized function of MDSCs is suppressing anti-tumor immune responses. Strikingly, these cells are among important players in cancer dissemination and metastasis. They can exert their effect on metastatic process by affecting anti-cancer immunity, epithelial–mesenchymal transition, cancer stem cell formation, angiogenesis, establishing premetastatic niche, and supporting cancer cell survival and growth in metastatic sites. In this article, we review and discuss the mechanisms by which MDSCs contribute to cancer metastasis.