Mouse models of lupus have for many years provided accessible and reliable research systems for the pathogenesis and therapy of systemic autoimmune disease, spanning a spectrum of inbred strains that develop spontaneous disease to experimentally induced, sometimes genetically manipulated animals. Nearly all the models share in common the development of glomerulonephritis and autoantibodies, including antinuclear and DNA specificities, the most common endpoints examined in experimental studies, but exhibit specific differences in the incidence of other end-organ manifestations such as hemolytic anemia, arthritis, dermatitis, and vasculitis. This chapter contrasts the clinical characteristics of these various models, providing an outline for their use and analysis.