The progressive destruction of articular cartilage is a hallmark of RA, a systemic autoimmune disease predominantly affecting synovial joints that often results in severe disability. Fibroblast-like synoviocytes (FLSs) have been demonstrated to play a key role in both the initiation and perpetuation of the disease. During RA pathogenesis, FLSs acquire a permanently aggressive, tumour-like phenotype that mediates cartilage destruction both directly and indirectly. This short review summarizes the recent advances in the understanding of FLS cellular transformation during RA, as well as the consequences for disease progression and for novel treatment strategies.