Abstract Rheumatoid arthritis (RA) is characterized by inflammation and proliferation of synovial tissue, leading to degradation of articular cartilage and bone with functional impairment as a result. It has recently become clear that early suppression of synovial inflammation is essential in preventing progressive joint destruction, although inflammation and destruction are in part uncoupled. New insights into the role of matrix metalloproteinases (MMPs), aggrecanase, granzyme B, receptor activator of nuclear factor κB (RANK)-receptor activator of nuclear factor κB ligand (RANKL) interaction, and other factors involved in joint destruction may lead to the development of novel therapies aimed at specific inhibition of cartilage and bone degradation.