Hepatitis C is a widespread chronic liver disease leading to cirrhosis and to the complications of portal hypertension. Based on biochemical and clinical features, it is almost indistinguishable from autoimmune hepatitis, which is characterized by the absence of viral infection, and other causes of chronic liver diseases, and represents a classical autoimmune disease with loss of immunological tolerance of liver tissue. Although the differentiation between both diseases is not difficult due the availability of diagnostic viral markers, it is well recognized that not only are autoantibodies present in autoimmune hepatitis frequently detected in hepatitis C, but also that an array of immune-mediated symptoms and diseases occur in patients with chronic hepatitis C. This has prompted research aimed at identifying a link between hepatitis C and autoimmunity, and autoimmune hepatitis in particular. This review focuses on the general immunological mechanisms linking viral infections with autoimmunity and includes the specific features of hepatitis C- and D-associated autoimmunity. Virus infection remains at the center of molecular and cellular research aimed at identifying the forces driving human autoimmunity and autoimmune diseases.