Osteoarthritis (OA) is the most common form of joint disease and the leading cause of chronic disability in middle-aged and older populations. The development of disease-modifying therapy for OA currently faces major obstacles largely because the regulatory mechanisms for the function of joint tissue cells remain unclear. Previous studies have found that the alterations in gene expression of specific transcription factors (TFs), pro- or anti-inflammatory cytokines, matrix proteinases and extracellular matrix (ECM) proteins in articular cartilage may be involved in the development of OA. However, the regulatory mechanisms for the expression of those genes in OA chondrocytes are largely unknown. The recent advances in epigenetic studies have shed lights on the importance of epigenetic regulation of gene expression in the development of OA. In this review, we summarize and discuss the recent studies on the regulatory roles of various epigenetic mechanisms in the expression of genes for specific TFs, cytokines, ECM proteins and matrix proteinases, as well the significance of these epigenetic mechanisms in the pathogenesis of OA.