Accumulation of fibrin in the synovium in rheumatoid arthritis (RA) exceeds that in control tissue by a wide margin and represents one of the most striking pathologic features of rheumatoid synovitis (1, 2). For some time, this fibrin deposition has been considered to be a serious contributor to permanent damage by maintaining a vicious circle of inflammation (1, 3). The extent of fibrin deposition in the joints most likely results from a local imbalance between fibrin formation and fibrin removal. Degradation of fibrin is primarily mediated by the serine protease, plasmin. The potential significance for RA of the accumulated fibrin and of the components of the pathways governing its formation and removal are discussed in this review. It is widely assumed that neutral proteases are involved directly in at least some of the inflammatory and destructive changes observed in RA; consideration is also therefore given in this review to additional roles in RA for plasmin in the inflammatory response and joint remodeling. Some potential therapeutic strategies are also considered.