Epigenetics examines heritable changes in DNA and its associated proteins except mutations in gene sequence. Epigenetic regulation plays fundamental roles in kidney cell biology through the action of DNA methylation, chromatin modification via epigenetic regulators and non-coding RNA species. Kidney diseases, including acute kidney injury, chronic kidney disease, diabetic kidney disease and renal fibrosis are multistep processes associated with numerous molecular alterations even in individual kidney cells. Epigenetic alterations, including anomalous DNA methylation, aberrant histone alterations and changes of microRNA expression all contribute to kidney pathogenesis. These changes alter the genome-wide epigenetic signatures and disrupt essential pathways that protect renal cells from uncontrolled growth, apoptosis and development of other renal associated syndromes. Molecular changes impact cellular function within kidney cells and its microenvironment to drive and maintain disease phenotype. In this chapter, we briefly summarize epigenetic mechanisms in four kidney diseases including acute kidney injury, chronic kidney disease, diabetic kidney disease and renal fibrosis. We primarily focus on current knowledge about the genome-wide profiling of DNA methylation and histone modification, and epigenetic regulation on specific gene(s) in the pathophysiology of these diseases and the translational potential of identifying new biomarkers and treatment for prevention and therapy. Incorporating epigenomic testing into clinical research is essential to elucidate novel epigenetic biomarkers and develop precision medicine using emerging therapies.