Systemic lupus erythematosus (SLE) is an uncommon childhood illness that is characterized by the formation of autoantibodies and immune complexes, which mediate inflammatory responses in multiple organ systems. Children who develop SLE are frequently very ill at the time of presentation and need careful evaluation to determine which organ systems are involved and how severely, meticulous control of medications to suppress active disease, and close monitoring to avoid complications from both the disease and its treatment.