Rheumatoid arthritis is an immune-mediated disease that primarily affects diarthrodial joints. Susceptibility and severity of this disease are influenced by nongenetic factors, such as environmental stress, suggesting an important role of epigenetic changes. In this review, we summarize the epigenetic changes (DNA methylation, histone modification and miRNA expression) in fibroblast-like synoviocytes, which are the joint-lining mesenchymal cells that play an important role in joint inflammation and damage. We also review the effects of these epigenetic changes on rheumatoid arthritis pathogenesis and discuss their therapeutic potential.