Activation of the complement system plays a fundamental role in the pathogenesis of systemic lupus erythematosus (SLE). For the past several decades, quantifying this process has focused primarily on determination of serum C3 and C4, although the utility of these assays for diagnosis and monitoring disease activity is still debated. During this same timespan, knowledge of the complement system has exploded, with identification of more than 30 proteins, an abundance of newly recognized functions, and even a third pathway of activation. These advances suggest that it is appropriate to revisit the complement system as a potential source of biomarkers for SLE. This paper reviews briefly the role of complement in SLE and other inflammatory diseases, discusses conventional methods for complement measurement and their drawbacks, and focuses on recent advancements in harnessing the complement system for monitoring SLE. Specifically, novel assays that measure cell-bound complement activation products are introduced and their utility as biomarkers of SLE disease activity is discussed.