The liver has an unusual capacity to regenerate after a loss of mass and function caused by surgical resection or toxic liver injury. Over the last 10 years there have been major advances in our understanding of the molecular and cellular mechanisms underlying liver development and regeneration. The numerous factors crucial to these phenomena have been identified mainly by using knockout mice. Forward-genetics studies using zebrafish and medaka have also generated many mutants with liver disorders or defects in liver formation. Our goal is to translate knowledge gained from laboratory work and animal models into novel therapies for human liver diseases. Exciting progress has been achieved using human partial liver transplantation and autologous cell therapy.