Improved understanding of the cellular and molecular basis of adaptive immunity has been realized over the past few decades, leading to the development of novel immunotherapeutic strategies capable of promoting host anti-tumor immunity. In order to achieve clinically meaningful results, further understanding of the mechanisms by which tumors suppress host immunity, and the development of therapeutic strategies which overcome tumor-associated immune suppression, will be necessary. Myeloid-derived cells with potent immunosuppressive properties are ubiquitous in human cancers. Improved mechanistic understanding of factors promoting their development, activation and mechanisms of immune suppression are being translated into novel therapeutic approaches, and will be summarized herein.