Few biomarkers for systemic lupus erythematosus (SLE) have been validated and employed for making clinical decisions. The lack of reliable, specific biomarkers for SLE hampers the proper clinical management of patients with SLE and impedes the development of new lupus therapeutics. This void has led to renewed enthusiasm for identifying biomarkers that precisely and specifically reflect the pathophysiological and clinical changes of SLE. Several laboratory markers have shown early promise as biomarkers for lupus susceptibility, diagnosis and monitoring. These include polymorphisms and copy-number variations of complement C4 and Fcgamma receptor genes (disease susceptibility), cell-bound complement C4d (diagnosis and/or disease activity), CD27(high) plasma cells (disease activity), 'interferon signature' (disease activity) and anti-C1q and anti-NMDA (disease activity and organ involvement). Although these and other promising candidate biomarkers have been identified, they still need to be validated through rigorous, large-scale multicentre studies. This article briefly reviews the historical aspects of lupus biomarkers and summarises current efforts to advance the field.