Rheumatoid arthritis (RA) is a chronic inflammatory disease that often results in significant morbidity, mortality and disability. Over the past 20 years a better understanding of the pathogenesis of RA has led to the development of new approaches to disease treatment. The recent introduction of biological agents has changed the treatment paradigm for RA. The success of early biological therapies including TNF-alpha and IL-1 antagonists has spurred interest in the development of additional novel targets in the treatment of RA. Biological therapies approved for other indications, such as rituximab, are now being evaluated for the treatment of rheumatic diseases such as RA. A co-stimulatory blocker, abatacept, is also in pivotal Phase III trials. This article reviews evolving pharmacological therapies in RA with an emphasis on the newer approaches to treatment including inhibition of cognate signalling and T- and B-cell targets.