Skin disease is the second most common manifestation in SLE patients, and a large number of patients have predominantly cutaneous lupus erythematosus. Experimental animal models suggest that modulation of immunologic factors can have a differential impact on the skin relative to the kidney, and therapeutic responses also suggest potential differences in the immunomodulation of skin relative to other organs affected in lupus. There have been recent insights into the etiology of cutaneous LE, including genetic and environmental factors. The growing understanding of the inflammatory cascade includes the role of UV-induction of pro-inflammatory cytokines, chemokines, and adhesion molecules. Apoptosis, necrosis, autoantibodies, plasmacytoid dendritic cells, T cells, B cells, and vascular changes all play a complex interactive role in the process of induction and maintenance of the lesions of cutaneous LE. Scientific efforts are beginning to clarify the pathophysiologic differences between subsets of cutaneous LE, but there are clearly many areas of investigation needed to elucidate the complex mechanisms that culminate in cutaneous LE.