Cytokines, chemokines, and growth factors are overexpressed by renal parenchymal cells and by infiltrating mononuclear cells in human and experimental lupus nephritis. The importance of cytokines in the pathogenesis of lupus nephritis has been established using spontaneous mouse models of systemic lupus erythematosus (SLE). The actions of these cytokines are complex. There is a growing appreciation that the cytokine level and stage of kidney disease determines whether cytokine protects or promotes further tissue injury. This article identifies potential therapeutic targets and strategies that might halt progressive renal injury in patients with SLE.