There are many types of ANA and they may react with different nuclear components varying from nucleic acids to both basic and acidic nuclear proteins. Recent investigations have demonstrated that it is important not only to detect the presence and quantity of the ANA, but also to identify the immunologic specificities of the ANA in a given patient. The specific identification of the immunologic specificity of the ANA helps in the diagnosis and management of therapy in the various rheumatic diseases. In recent years, much progress has been made in the improvements of sensitivity, specificity, and quality control of many of the clinical laboratory tests for detection and quantitation of ANAs. Distinct profiles of ANA characterize different rheumatic diseases. A number of ANAs are found in SLE, whereas other diseases are characterized by the presence or absence of a certain ANA or by differences in mean ANA titers. Specific ANAs have been used to isolate and characterize nuclear antigens at the molecular and functional levels.