Myeloid cells are extremely plastic as they respond and terminally differentiate into a plethora of functional types, in the blood or tissues, in response to a variety of growth factors, cytokines and pathogenic molecules. This plasticity is also manifested by the subversion of normal differentiation into the aberrant generation of a variety of tolerogenic myeloid cells in the tumoral microenvironment, where a variety of factors are released. Epigenetic mechanisms are in great part responsible for the plasticity of myeloid cells both under physiological and tumoral conditions. The development of compounds that inhibit epigenetic enzymes provides novel therapeutic opportunities to intercept the crosstalk between cancer cells and host myeloid cells. Here, we summarize our current knowledge on the myeloid cell types generated in the cancer environment, the factors and epigenetic enzymes participating in these processes and propose a number of potential targets for future pharmacological use.