Chondrocyte dysfunction is attributable to the development of osteoarthritis (OA). Deregulation of chondrogenic regulators and deleterious factors, e.g. proteinases, Wnt signalling components, and autophagy repressors lowers chondrogenic activities and ultimately deteriorates cartilage homeostasis. Emerging evidence is that epigenetic pathways, including non-coding microRNAs and histone remodelling switch on/off the expression of joint-deleterious factors. MicroRNAs reduces the expressions of mRNAs through binding to the 3'-untranslation regions of targets. The levels of microRNAs, e.g. miR-29a, miR-128a in serum, synovial fluid, synovium, and cartilage are correlated with the occurrence of OA. Mice overexpressing/deficient microRNAs of interest show minor responses to OA progression. Besides, acetylation and methylation statuses of histones regulate the factors detrimental to chondrocytes through altering the interactions between histones and promoters. Histone deacetylases and demethylases, e.g. HDAC4, SIRT1, and EZH2 contribute to the modification reactions of histones, which modulate cartilage matrix metabolism. An intricate nature is that reciprocal actions between microRNAs and histone deacetylase/demethylase are indispensable in chondrocyte survival and function. Administrations with specific inhibitor/agonists for microRNAs and histone deacetylases/demethylase enable joints to show minor responses to articular injury, which mitigate the pathogenesis of OA. This talk highlights the biological roles and therapeutic advantage of epigenetic microRNAs and histone remodelling in OA