The cells in a human body have identical DNA sequences, yet the body has >200 cell types with different phenotypes. The basis for this nongenetic cellular memory, which records developmental and environmental cues, is epigenetics. The epigenome includes covalent modifications of the DNA and its associated proteins and defines DNA accessibility to the transcriptional machinery. Notably, the epigenome has emerged as an important mediator of the long-term programming effect of environmental exposure, and multiple lines of evidence point to the epigenome as an important missing link in our understanding of CKD development. For example, recent studies identified epigenetic differences in the enhancer regions of fibrosis-related genes in diseased human kidney samples. Furthermore, chromatin profiling and epigenome analysis are powerful tools for annotating gene regulatory regions that can be harnessed to interpret disease-causing polymorphisms for complex traits such as CKD. This review highlights the results of studies investigating the renal epigenome and discusses the significance of these findings and future directions in the context of novel diagnostic and treatment strategies for CKD.