OBJECTIVES: To systematically review the current literature relating to the cost-of-illness (COI) of rheumatoid arthritis (RA). METHODS: Medline, Embase, BIOSIS, Derwent Drug File, the Cochrane library and NHS-EED were searched on 12th March 2007. Original studies (2002-present) reporting COI data were included after a two-stage review process. Bibliographies of included studies were also searched for additional citations. Data were extracted into predefined extraction grids and were analysed using Microsoft Excel. RESULTS: Nine hundred and nine unique citations were retrieved. Of these, 9 studies presented COI results. These studies were conducted in 5 different countries (Australia, France, Germany, Sweden, and the US) from 2003-2007. Six studies adopted a societal perspective by including direct medical and non-medical costs and indirect costs. Patient populations across the studies ranged from only early RA (<12 months from disease onset) to all RA patients. The use of biological agents (including infliximab, etanercept, and anakinra) was assessed in only 3 of these studies. Annual direct costs ranged between €3000 and €4000 in all European countries. Lower annual direct costs were reported in the Australian analysis as a result of the inclusion of all Australian adults with RA, while substantially higher costs were found in a US study. This could be attributed to the higher costs of medications that included anti-TNF therapies. In terms of components of direct costs, medications and hospitalisations were generally the categories associated with the highest costs. Indirect costs exceeded direct costs in 5 of the 6 analyses. These ranged between 2 and 4 times the direct costs. Finally, a statistically significant positive correlation was found in most studies between total RA costs and disease severity. CONCLUSION: This review of recently published COI analyses found that RA is associated with significant direct and indirect costs, with the economic burden being highly dependent on the level of functional disability.