Experimental models of rheumatoid arthritis have contributed immensely to our understanding of the pathogenesis as well as the treatment of this debilitating autoimmune disease. Significant progress has been made in the past few years in defining the role of newer cytokines and regulatory T cells, of inflammation-mediated bone and cartilage damage, and of the cholinergic anti-inflammatory pathway in modulating the disease process in arthritis. Furthermore, new therapeutic targets, including specific tyrosine kinases and proteasome subunits, have been explored. These advances offer renewed optimism for continued improvements in the management of rheumatoid arthritis.