Biliary atresia (BA) is the most common and important neonatal hepatobiliary disorder. Because current treatment is inadequate, there is an urgent need to better understand the etiology and pathogenesis of BA. Two major forms of BA are recognized: an embryonic form associated with other congenital anomalies and a perinatal form in which bile ducts were presumably formed normally but underwent fibro-obliteration in the perinatal period. There are currently several proposed pathogenic pathways leading to the phenotype of BA, including an immune or autoimmune response to a perinatal insult (e.g. cholangiotropic viral infection) and dysregulated embryonic development of the extra- or intrahepatic biliary system. Recent advances in developmental biology, genomics and genetics, and cell immunology and biology, coupled with the development of appropriate animal models, have provided support for these postulated mechanisms. Future investigations combining animal model work and evaluation of clinical specimens holds the promise of identifying the etiology of BA and providing a scientific basis for treatment and preventative interventions.