A large amount of descriptive data on the morphogenesis of the biliary tract has been collected in the past two decades. These studies identified a number of molecules as candidates for the control of biliary differentiation and morphogenesis, based on the observation that their expression correlates with one or another step of biliary development. The recent identification of genes responsible for human diseases and the phenotypic analysis of transgenic mice have demonstrated the involvement of transcription factors and signalling pathways in biliary development. New transgenic mice should allow to test the role of additional proteins. We have also underlined how tightly the development of bile ducts, portal vasculature and portal mesenchyme is cross-regulated. Thus, culture systems that maintain an association between ducts, blood vessels and mesenchyme are required to further elucidate the mechanisms controlling bile duct development. Unravelling these mechanisms is critical to understand the pathogenesis of human biliary malformations.