Animal models have played a critical role in the history of modern drug development for rheumatoid arthritis (RA). In this chapter I examine the contributions of animal models in arthritis therapy from adjuvant arthritis and COX-1 inhibitors to transgenic mice and biological response modifiers. Advances in knowledge of the mechanisms of connective tissue disease are frequently derived from the study of animal models, and these findings frequently identify therapeutic targets that are subsequently evaluated in animal models. Hence a critical relationship between insights into the pathology of arthritis and the development of novel therapeutic approaches exists around the study of animal models of arthritis. In particular, we examine how the study of collagen-induced arthritis in rodents led to pioneering work in cytokine inhibitors for the successful therapy of RA.