Measuring lupus disease activity accurately remains a challenging and demanding task given the complex multi-system nature of lupus, an illness known for its variability between patients and within the same patient over time. Many have attempted to define what disease activity means and how it should be measured, and several instruments were devised for a standardized assessment of disease activity and outcome domains in clinical research. Several of these measuring tools have been able to detect clinical improvement and have demonstrated adequate reliability, validity, and sensitivity to change in observational studies, and some were found to be useful in randomized controlled trials. However, several failed clinical trials have confronted these metrics, as they were not intended for clinical trials. The Outcome Measures Rheumatology group and the US Food and Drug Administration have recommended using measures of disease activity, cumulative organ damage, health-related quality of life, and adverse events as outcomes of interest. Composite responder indices that determine disease global improvement, ensure no significant worsening in unaffected organ systems, and include a physician's global assessment have been used in randomized clinical trials. Yet unmet therapeutic needs were further challenged by the complex content and psychometric information of the updated instruments, including increased administrative burden associated with demanding training and cost of instruments, and small effect size associated with responsiveness to patient concerns. Nevertheless, with the progress of novel targeted therapy, refining the disease activity metrics is essential. Selection of the disease activity endpoints which is a defining aspect of clinical trial design must be tailored to the outcome of interest and measured by a reliably rated scale characterized by minimal administrative burden. An optimal scale should be simple and practical and incorporate elements of patient concerns.