Organ fibrosis is a complex and chronic disorder that results from a variety of acute injuries and contributes to thirty percent of naturally occurring deaths worldwide. The main feature of organ fibrosis is the excessive accumulation and deposit of extracellular matrix, thereby leading to organ dysfunction, loss of elasticity, and development of a rigid organ. Accumulating evidence shows that epigenetic remodeling, including aberrant DNA methylation and noncoding RNA expression as well as histone post-translational modifications, play important roles in the pathogenesis of fibrosis through the regulation of fibroblast activation, differentiation, and apoptosis, as well as collagen synthesis and profibrotic gene transcription. In this review, we discuss the basic regulation of DNA methylation, noncoding RNA expression, and histone post-translational modification, and their participation in the pathogenesis and development of organ fibrosis. This review also provides the latest insights into the novel biomarkers and therapeutic targets for fibrosis through modulation of epigenetic remodeling.