There is no serologic test that reliably measures disease activity in systemic lupus erythematosus (SLE). The 'gold standard' is the anti-dsDNA antibody test, which has been used as a marker of disease activity by clinicians in SLE for over 35 years. Anti-dsDNA antibodies perform best in those with lupus nephritis, specifically in the presence of a proliferative lesion [World Health Organization (WHO) class III or IV] on renal biopsy. In one recent meta-analysis, the mean positive likelihood ratio of anti-dsDNA antibodies as a marker of disease activity in SLE was 4.14, implying the overall predictive effect was small. More recently autoantibody assays have been developed that show greater promise in gauging SLE disease activity, specifically anti-nucleosome and anti-C1q antibodies (especially with renal disease activity). Other tests thought previously to be lacking in specificity that refinements in ELISA technology now render possibly useful include anti-heparan sulfate, anti-ssDNA and anti-Scl-70 autoantibodies. Other tests that as yet have not been shown to be as reliable (and therefore are not as useful in clinical practice for serial determination to measure disease activity) include other anti-extractable nuclear antibodies (anti-Ro, La, Sm, RNP), anti-cardiolipin antibodies, and anti-nuclear cytoplasmic antibodies (ANCA). New technologies using proteomic determinations show promise as aids in the search for more reliable and feasible autoantibody determinations of disease activity in SLE.