In this article, assessment of disease activity in systemic lupus erythematosus (SLE), including available instruments and their use in patients with SLE, is discussed. Several validated measures, including the SLAM (Systemic Lupus Activity Measure), SLEDAI (Systemic Lupus Erythematosus Disease Activity Index), LAI (Lupus Activity Index), ECLAM (European Consensus Lupus Activity Measurement), and that of the BILAG (British Isles Lupus Activity Group) are now available and should be included in studies of new laboratory measures, therapeutic trials, and studies of outcome and prognosis. The prognosis of SLE has improved over the past 4 decades, including 20-year survival rates. With improved survival, other outcome measures such as specific organ function and health status need to be considered. Administration of hydroxychloroquine remains an important part of therapy for SLE. The use of cyclophosphamide should be reserved for severe manifestations of the disease. Newer forms of therapy, particularly immunotherapy, have been tested in animal models.