In recent years, epigenetics has emerged as important mechanisms for the regulation of pathogenesis in many diseases, including acute kidney injury (AKI). Numerous studies have demonstrated that AKI is associated with the changes in epigenetics, including histone modifications, DNA methylation and the expression of various non‐coding RNAs. Through utilizing histone deacetylase (HDAC) inhibitors, studies have demonstrated that increase of histone acetylation either protects kidney from injury or potentiates this process, depending on which HDAC (s) isform is suppressed, whereas inhibition of histone methyltransferase, generally provides a protective effect in AKI. Although AKI is also associated with changes in DNA methylation, the role of DNA methylation in kidney injury remains unclear. In this article, we discuss the role and mechanism of histone acetylation and methylation in the pathogenesis of AKI.