Bone loss in RA includes juxta-articular osteopenia, erosions and systemic osteoporosis. In each case, synthesis of new bone matrix is unable to balance osteoclast-mediated bone resorption, resulting in net bone loss. IL-1, TNF and other proinflammatory cytokines stimulate osteoclast differentiation and activation, resulting in bone loss. In addition, these proinflammatory cytokines stimulate synovial fibroblasts and chondrocytes to produce proteinases that degrade cartilage. In animal arthritis models, blocking IL-1 significantly reduces bone erosions and cartilage degradation, whereas blocking TNF decreases synovitis. In patients with active RA, treatment with the TNF blockers etanercept and infliximab, as well as with anakinra, a recombinant human IL-1 receptor antagonist, significantly reduced erosions and joint space narrowing. It remains to be determined, however, whether slowing radiographic progression with these biological therapies will significantly improve long-term outcomes in RA.