The destruction of articular structures in the course of inflammatory arthritides such as rheumatoid arthritis (RA) or seronegative spondyloarthropathies is the most serious direct consequence of these diseases. Indeed, joint damage constitutes the "organ damage" of RA and-just like in all other diseases with organ involvement-such damage will usually be irreversible, cause permanent loss of function and subsequent disability. Research has identified a number of mechanisms and mediators of damage to articular structures such as bone and cartilage, ranging from proinflammatory cytokines, signal transduction pathways and cells types, which will be discussed in this review.