Testing for autoantibodies is an integrated part in the diagnostic process of many autoimmune diseases. As a consequence, the detection of autoantibodies is increasingly recognized in classification criteria and diagnostic guidelines. In this review, the question is addressed whether quantification of autoantibodies is clinically useful, not only in the diagnostic stage, but also during follow-up of patients with autoimmune diseases. It can be concluded that for a multitude of autoantibodies, there is sufficient evidence that the higher the amount of autoantibodies, the more likely that the patient has the respective autoimmune disease. Quantification is also of added value for monitoring therapeutic efficacy, although this depends on the type of therapy that is installed. The relation between rises in autoantibody levels and the occurrence of subsequent disease relapses, however, is far from absolute. Obviously, if quantification of autoantibodies is performed in the laboratory, results should also be reported quantitatively together with an appropriate interpretation for the clinician.