Biliary atresia is the most common cause of neonatal cholestasis and the leading indication for pediatric liver transplantation worldwide. The disease is caused by a progressive inflammatory and fibrosing obliteration of the extrahepatic bile ducts. Although the cause of this obstruction is largely unknown, patient-based studies have identified environmental and genetic factors that may interact and orchestrate disease pathogenesis. Chief among these factors are infectious and immunologic processes. While infectious agents have varied in different patient populations, studies of liver specimens at different phases of disease point to a pro-inflammatory commitment of lymphocytes at the time of diagnosis, and to their potential role in regulating bile duct obstruction. A review of these studies is the focus of this article.