Liver fibrosis and its end stage, cirrhosis, represent the final common pathway of virtually all chronic liver diseases. As our understanding of the pathogenesis of liver fibrosis has progressed, it has become evident that the liver provides a useful generic model of inflammation and repair, demonstrating interplay between the epithelial, inflammatory, myofibroblast and extracellular matrix components of the mammalian wound healing response. In this review, the paradigm that liver fibrosis is a potentially reversible process—demonstrating both fibrosis (scarring) and resolution with remodeling and restitution of normal or near-normal tissue architecture—will be explored. The remarkable progress in unraveling the complexities of liver fibrosis has been due to developments in technologies including the isolation of discrete liver cell populations which have facilitated studies of their behavior in tissue culture and in vivo. More recently, animal models that mimic chronic liver diseases have been established. These models are tractable and can be applied in gene knockout and transgenic mice. This article will highlight recent studies that reveal key mechanisms mediating the regression of liver fibrosis which have derived from the use of such complementary animal and human model systems and describe how our greater understanding of this dynamic process is likely to inform the development of directed and effective anti-fibrotic approaches.