Autoimmune hepatitis (AIH)was first studied under its earlier name of chronic active hepatitis (CAH) from the 1950s, coincident with a renaissance of interest in autoimmunity. The definition of autoimmune serumreactants in disease, including CAH, gave new insights into chronic hepatitis and liver cirrhosis, and led to refinements of Burnet s clonal selection theory of acquired immunity, 1957a??59. Various discoveries including serological reactants in CAH prompted its designation in 1965 as autoimmune hepatitis, and treatment with immunosuppressive drug regimens transformed outcomes and survival. Serological observations further indicated that AIH could exist as either of two types, clinically similar but genetically different: Type 1 aligned morewith the non-organ-specific multisystem diseases, and the infrequent Type 2 morewith the organ-specific diseases. However, events in either type that could explain the onset of autoimmunity in the normally tolerogenic milieu of the liver have not been discerned. In the genetically predisposed individual, initiation may depend on non-specific death of hepatocytes after which fragments derived from disordered apoptosis acquire the capacity for ongoing auto-immunogenic stimulation. Insufficiency in numbers and function of Treg populations appears important in the promotion of this autoimmune process.