This article reviews past and present prescribing patterns for patients with rheumatoid arthritis and reveals some striking differences over time. For many practitioners, methotrexate has become the centerpiece around which other therapies are built; however, we are still learning a great deal about this drug. In this article, some recent advances are described. The prospects for further therapeutic development are discussed, with a focus on the present state-of-the-art combination chemotherapeutic regimens. Consideration is given to ways in which new approaches might facilitate clinical research in this severely underfunded area.