Detection of antinuclear antibodies (ANA) is of growing relevance in the management of connective tissue diseases (CTD). ANA are useful diagnostic tools, since most CTD have a peculiar ANA profile, characterized either by restricted specificities, abnormally high titers, or both. Furthermore, the study of the intimate structure and function of nuclear antigens, and of their corresponding antibodies may provide important insights to understand both origin and pathogenesis of CTD. Finally, the more or less close association of ANA levels and/or specificity with certain signs or symptoms of CTD is of increasing help to the clinician in the correct monitoring and management of CTD.