The renal response to injury is mediated by a wide variety of cytokines and growth factors. This review provides a simplified schema in which the mediators are grouped into four categories: proinflammatory cytokines, vasoactive mediators, growth factor/matrix modulating molecules, and protease/matrix proteins that modulate cell behavior. Included are examples of how each group of mediators affect renal injury. Also discussed are the problems of modulating the cytokine response, including the problems of compensation or redundancy, modulating cytokines that have multiple actions, the consequences of partial versus complete blockade of a cytokine, and modifying renal disease when the renal injury in heterogenous. Despite these concerns, the recent progress in cytokines in disease pathogenesis is very likely to lead to new treatments of kidney disease.