Autoantibodies to double-stranded DNA (dsDNA) are, by definition, serological markers of systemic lupus erythematosus. However, the clinical value of anti-dsDNA antibodies largely depends on the assay principle and analytical variables of the methods used to quantitate and immunologically characterize them. In the present article, an overview of current methods for anti-dsDNA antibody detection is presented, together with a look at the future trends in technologies newly employed in this field.