Recent studies using animal models have elucidated a growing number of evolutionarily conserved genes and pathways that control liver development from the embryonic endoderm. It is increasingly clear that the genetic programs active in embryogenesis are often deregulated or reactivated in disease, cancer, and tissue repair. Understanding the molecular control of liver development should impact diagnosis and treatment of pediatric and adult liver diseases and aid in efforts to differentiate liver tissue in vitro for stem cell-based therapies.