Diseases produced by protozoa parasites are still a public health problem in the entire world. These parasites should have a severe control on the expression of genes involved in their development and pathogenicity. Epigenetic mechanisms through chromatin modifications performed by histone-modifying enzymes as well as DNA methylation could be involved in the expression regulation of those genes. The identification and characterization of the enzymes that achieve the chromatin modifications could help to develop novel therapeutic strategies against protozoa parasites. Here, we review the current understanding of the histone-modifying enzymes and DNA-methyltransferases in different protozoa parasites.