SLE presents many challenges for clinicians. The onset of disease may be insidious, with many different symptoms and signs, making early and accurate diagnosis challenging. Tests for SLE in the early stages lack specificity; those that are useful later often appear only after organ damage is manifest. Disease patterns are highly variable; flares are not predictable and not always associated with biomarkers. Children with SLE may have severe disease and present special management issues. Older SLE patients have complicating co-morbid conditions. Therapeutic interventions have improved over recent decades, but available drugs do not adequately control disease in many patients, and successful outcomes are limited by off-target effects; some of these become manifest with longer duration of treatment, now in part revealed by improved rates of survival. Despite all of these challenges, advances in understanding the biological basis of SLE have translated into more effective approaches to patient care. This review considers the current state of SLE diagnosis and management, with a focus on new approaches and anticipated advances.