Introduction of biological agents for the treatment of the chronic inflammatory joint disease rheumatoid arthritis has reinvigorated research into this debilitating disease. These agents have been shown to both act on the signs and symptoms of disease, as well as retard the progression of joint destruction. However, these agents are not efficacious in all cases and their expense and route of administration can severely limit their use. Therefore the search continues not only for additional targets to help those individuals refractive to current therapy but also for more affordable orally active small molecule alternatives to biological agents.