Commensal microorganisms colonize barrier surfaces of all multicellular organisms, including those of humans. For more than 500 million years commensal microorganisms and their hosts have coevolved and adapted to each other. As a result, the commensal microbiota affects many immune and non-immune functions of their hosts, and de facto the two together comprise one metaorganism. The commensal microbiota communicates with the host via biologically active molecules. Recently, it has been reported that microbial imbalance may play a critical role in the development of multiple diseases, such as cancer, autoimmune conditions and increased susceptibility to infection. The commensal microbiota not only may affect the development, progression and immune evasion of cancer but it has also important effects on the response to cancer immune- and chemo-therapy. Myeloid cells are a major component of the tumor microenvironment where they play a dual role inducing anti-tumor immune responses but mostly promoting immune evasion, tumor progression and metastases formation. Myeloid cells respond to environmental factors including signals derived from commensal microbes that modulate their function and reactivity thus impacting the response to cancer therapy.