Biomarker development in lupus nephritis (LN) has traditionally relied on comparing the characteristics of candidate markers to clinical findings in patients and controls from cross-sectional cohorts. In this work, two additional strategies for LN biomarker development that are gaining ground will be discussed. One approach compares analytes directly to kidney histology. The second strategy utilizes longitudinal measurements of biomarker levels at regular intervals as patients move from disease quiescence to disease flare. These approaches have begun to empower biomarkers as diagnostic and prognostic tools in LN and have revealed novel and sometimes unexpected roles for these biomarkers in the pathogenesis and prediction of LN disease activity.