Systemic lupus erythematosus (SLE) is the archetypal autoimmune disease given its complex clinical and molecular manifestations. Like the other rheumatic diseases, appropriate management is critically dependent upon the proper assessment of disease activity, organ damage, and quality of life. Here, we describe the components of the comprehensive assessment of SLE, including accurate physical and laboratory diagnosis, monitoring of disease activity, recording of accumulated organ morbidity, and integration of these with the patient's own perceptions of health status and quality of life. In doing so, we will review the most appropriate laboratory tests and indices currently used in standard clinical care and in clinical research.