OBJECTIVES New therapeutic options for rheumatoid arthritis (RA) have shifted the focus of treatment to early, aggressive intervention aimed at preventing further joint damage. However, early diagnosis has proved challenging, and recent efforts have been made to identify new diagnostic tests. We systematically reviewed the literature to assess the current status of tests for early diagnosis of RA. METHODS We searched English-language MEDLINE-indexed publications in the 5 years prior to August 2008 concerning tests and biomarkers for early diagnosis of RA. We also searched non-MEDLINE-indexed sources such as organization websites, meeting abstracts, and governmental publications using the same keywords. RESULTS We identified 94 primary studies from MEDLINE pertaining to tests or biomarkers for early diagnosis of RA. Non-MEDLINE sources yielded an additional 56 articles for a total of 150 reviewed for this study. In practice, no single test has proved sufficiently sensitive and specific for the diagnosis of RA. Tests currently in use, including the acute phase biomarkers erythrocyte sedimentation rate and C-reactive protein and the autoantibody rheumatoid factor (RF), are relatively nonspecific for RA. Recent efforts have focused on identifying new biomarkers with greater RA specificity. These include many autoantibodies, immune system biomarkers, and biomarkers of collagen breakdown and bone erosion. The autoantibody anti-cyclic citrullinated peptide (anti-CCP) offers high specificity, but lower sensitivity than RF. Newer-generation anti-CCP assays provide improved sensitivity over first-generation anti-CCP assays, but sensitivity still precludes their use as sole diagnostic tests for RA. The clinical utility of anti-CCP tests can be improved by combining with other assays such as RF, and provide particular value in predicting the development of persistent and/or erosive RA. CONCLUSIONS Newer generations of the autoantibody anti-CCP assay offer high specificity for RA and appear promising as a diagnostic test in combination with other tests with greater sensitivity.