Epigenetics defines the cellularly heritable properties of genome function, which are not directly encoded in the DNA primary sequence. The underlying mechanisms orchestrate cell identity and memory and are targets for external and internal environmental influences. It becomes increasingly clear that genetic and epigenetic factors are completely interdependent for homeostasis. Subsequently, the same is certainly true for disease. Our understanding of epigenetic mechanisms in chronic kidney disease (CKD) is still lagging, and further studies are needed to understand the importance of, e.g., aberrant DNA methylation in relation to the uremic impact on the functional genome, organismal metabolism and associated premature vascular disease. More research in this field will also help us understand the links between altered gene regulation of specific genes by the uremic environment via epigenetic mechanisms, and initiation and progression of atherosclerosis. The dynamic nature of epigenetic mechanisms prompts therapeutic investigations in CKD, targeting the epigenome with epigenetic drugs. The importance of 1-carbon metabolism for epigenetic modifications suggests that specific diets may also prove to play an important part as efficient remedies in CKD and associated atherosclerotic pathologies.