The presence of autoantibodies in apparently healthy individuals has been increasingly recognized. Although some of these individuals are in preclinical stages of a disease such as systemic lupus erythematosus (SLE), many will not develop SLE or any other autoimmune disorder. The high prevalence of autoreactivity in the population in fact suggests that autoantibodies are expressed as part of a healthy immune response, and other data have clearly shown that some autoantibodies have important immune regulatory functions. These observations leave open questions regarding when and how benign autoimmunity develops into disease. If the transition from preclinical autoimmunity to a clinical disorder such as SLE could be predicted, early and thus potentially more effective intervention might be possible and cures might even become a reality. Furthermore, increased understanding of mechanisms by which autoantibodies are kept in check can identify new approaches to aborting or preventing disease transformations. In this article, we summarize the current findings regarding the presence of SLE-associated antibodies in apparently healthy individuals, and provide our opinions on what such discoveries might tell us about the roles of autoantibodies in the development of disease.