Both immune and nonimmune mechanisms are operant in lupus nephritis. Recent findings have begun to elucidate fundamental questions in the pathogenesis of the disease. Genetic linkage studies have identified susceptibility loci contributing to nephritis in lupus-prone mice. Polymorphisms of the Fc gamma Rlla gene have been found to correlate with the development of renal disease in black Americans and white Europeans. Genetic factors are important in determining both predisposition to nephritis and outcome (and likely response to therapy). In lupus nephritis, prevention of tissue injury involves effective immunosuppressive therapy and aggressive management of hypertension and hyperlipidemia. Although with intensive immunosuppressive therapy most lupus patients achieve remission, a substantial number of these patients either do not respond, respond partially, or relapse after discontinuation of therapy. Moreover, the toxicity of available immunosuppressive drugs is substantial, suggesting that alternative therapeutic regimens are needed. In the future, other inhibitors of inflammatory, immune, vasoactive, proteolytic, and growth-promoting mediators are likely to play a role in the management of lupus nephritis.