Cancer has historically been viewed as a disease determined by genetic and environmental factors, however, it is now clear that inflammation affects all stages of the disease: initiation, progression and metastasis formation. The inflamed tumor microenvironment is in part sustained by infiltrating mononuclear phagocytes (MPs) [e.g. dendritic cells, monocytes, macrophages] and neutrophils. In cancer, as in infection, MPs can induce adaptive immune responses, but in cancer they mainly promote the tumor’s immune evasion, progression, and metastasis. We, and others, have recently uncovered a role for commensal microbes in controlling the response of subcutaneous tumors to cancer immuno- and chemotherapy. In this presentation, we will discuss the role of the microbiota in regulating the composition and function of the myeloid cell compartment in the tumor microenvironment and the role of these cells in the response to cancer chemotherapy. Targeting MPs represents a powerful approach to manipulate the outcome of immune responses; therefore, a clear understanding of their regulation and functional organization may lead to rational novel cancer immunotherapeutic approaches.