Epigenetics is a discipline that for many years has languished in the shadow of its genomic big brother. Because our understanding of the role played by epigenetics in chronic kidney disease remains in its infancy, further studies are needed to understand the associations, for instance, of aberrant DNA methylation in relation to uremic dysmetabolism, and its presumably very complex interactions in the development of premature uremic vascular disease. Further research is also needed to study the association between aberrant global DNA-methylation, gene-level methylation status, and the silencing (or activation) of candidate genes associated with atherosclerosis. Insofar as it seems possible to manipulate the epigenome, the effects of various epigenetic-targeted and pathway-targeted therapeutic approaches on unbalanced DNA methylation, gene silencing, and vascular health and outcomes should be explored further in uremia.