Hepatic fibrosis is the scarring response of the liver to chronic liver injury; when fibrosis progresses to cirrhosis, morbid complications can develop. Available therapies for many chronic liver diseases are ineffective, with liver transplantation as the only option, though the supply of donor organs is inadequate to meet the growing demand. Novel approaches that attack the scarring response are therefore urgently needed. Optimism in this effort is fueled by major insights into the pathogenesis of fibrosis and by accumulating evidence that even cirrhosis is reversible in many patients. Most evolving antifibrotic therapies will be aimed at inhibiting the activated hepatic stellate cell, which is responsible for the fibrotic response to injury. This review describes the ways in which insights into the cellular basis of hepatic fibrosis are leading to realistic strategies for antifibrotic treatment that may revolutionize the management of patients with chronic liver disease.