Epigenetic modifications in rheumatoid arthritis synovial fibroblasts contribute to their aggressive phenotype. Rheumatoid arthritis synovial fibroblasts (RASF) are characterized by excessive activation and an apoptosis-resistant phenotype, leading to hyperplasia of the synovium. Furthermore, RASF are capable of producing chemokines and cytokines, and thereby promote inflammation. The production of matrix metalloproteinases (MMPs) leads to invasion of RASF into cartilage. These characteristics of RASF contribute to the hallmarks of RA, namely joint destruction, loss of function, disability and pain. Changes in epigenetic modifications, such as DNA methylation, histone acetylation, histone methylation, and histone sumoylation, were described in pathologically activated RASF.