A well-accepted view holds that the pathogenesis of rheumatoid arthritis (RA) and osteoarthritis (OA) differs. However, recent evidence has also indicated that similar focal and systemic alterations exist in RA and OA, leading us to postulate that there may well be a ‘final common pathway’ for arthritis. Thus, synovial tissue and articular cartilage responses to activated T and B cells, NF-κB and AP-1 activation, proinflammatory cytokines, growth hormone, chemokines, matrix metalloproteinases and hydrolytic cathepsins often act concurrently and synergistically to generate RA and OA pathology in which articular cartilage destruction is uncoupled from cartilage repair. However, there are also several critical areas in which RA and OA differ. These include the prominent involvement of synovial tissue angiogenesis and fibrin deposition in RA and, most notably, in the timing and extent of subchondral bone responses. Thus, irreversible bone erosion occurs in RA, whereas subchondral bone sclerosis with synovial joint remodeling is typically characteristic of OA.