Autoimmune liver diseases (ALD) are characterized by immune-mediated injury of bile ducts or hepatocytes, thus including cholangiopathies such as primary biliary cirrhosis (PBC), primary sclerosing cholangitis, and autoimmune hepatitis. Further, ALD variants manifesting with both hepatocellular and cholangiocellular damage are becoming more common. Serum autoantibodies, together with imaging and histology, are critical to the diagnostic process when ALD is suspected. Because an early diagnosis can influence prognosis, the development of sensitive and specific tests for serum autoantibodies should be a priority for researchers to ensure a more efficient noninvasive workup. Little prognostic value has been observed for any of the ALD serum hallmarks, and a vigorous effort to investigate new and old markers should therefore be undertaken in longitudinal studies as in the recent paradigm of PBC-specific antinuclear antibodies. We review herein the numerous ALD screening tests available in routine and specialized laboratories and comment on their significance in clinical practice.