Lupus is a serious, potentially life-threatening disease. Its natural history is to culminate in a crescendo of autoimmunity and organ involvement. Difficulty arriving at the diagnosis may delay institution of therapy, which although helpful brings new problems. The fundamental understanding of this disease has made major strides. There is no consensus on the likely etiological agent(s), though evidence implicates Epstein-Barr virus, and the genetic approach to understanding etiology is in its infancy. Nevertheless, efficacious treatments are anticipated in the plethora of new biologics likely to have therapeutic effects in lupus, essentially a disease of immune dysregulation.