Cytokines play a major role in the development of hepatic fibrosis, the wound-healing response of the liver to chronic injury. Major concepts in defining the role of cytokines in fibrogenesis include (1) Cytokines may be pro-or antifibrogenie;(2) autocrine, paracrine, and matrix-bound sources of cytokines are the most important; and (3) multiple mechanisms of cytokine regulation are essential to fine-tune their effects. The hepatic stellate cell is the key effector of the fibrotic response and both a principal source and target of cytokines. Activation of stellate cells connotes the conversion of a resting vitamin A-rich cell to one which is proliferative, contractile, fibrogenic, and devoid of vitamin A. The features of stellate cell activation provide a framework in which to understand how cytokines drive fibrosis. These features include (1) proliferation;(2) contractility;(3) fibrogenesis;(4) extracellular matrix degradation;(5) chemotaxis;(6) cytokine release; and (7) retinoid loss. The insights gained from illuminating the role of stellate cells has engendered realistic hopes for treating hepatic fibrosis through modulation of cytokine actions.