Increased knowledge about the mechanisms of joint inflammation and damage has profoundly shaped the development of new therapies for rheumatoid arthritis (RA). The first stop on this remarkable bench-to-bedside journey has been the biologics targeting tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 (IL-1). These engineered adaptations of naturally occurring molecules function to neutralize the biological activity of proinflammatory cytokines overproduced in the joints of patients with RA. The successful translation of this approach into the clinic has had a substantial effect on the care of patients with RA.