Increasingly, assays for the detection of anti-citrullinated peptide antibodies (ACPA) are used in RA diagnosis. This review summarizes the biologic basis and development of ACPA assays, available ACPA assays and their performance characteristics, and diagnostic properties of ACPA alone and compared to rheumatoid factor (RF) in early RA. We also review correlations, precision, costs and cost-effectiveness, availability, stability and reproducibility of the available assays. Taken together, data indicate that ACPA has a higher specificity than RF for early RA, good predictive validity, high sensitivity, apparent cost-effectiveness and good stability and reproducibility. Given its superior performance characteristics and increasing availability, ACPA is emerging as the most useful single assay for the diagnosis of RA.