Several studies have shown that autoimmune diseases are preceded by a long pre-clinical phase, and that many autoantibodies can be detected in the serum of asymptomatic subjects years before the clinical manifestations become evident. Tests for these autoantibodies could therefore be used in principle in screening studies on unselected populations to identify individuals predisposed to the development of the disease at an early stage, and start treatment or adopt preventive measures where possible. This aspect has aroused particular interest, as multiplex investigation techniques are already available, and microarray methods are under development, which will probably allow tens or hundreds of autoantibodies to be measured simultaneously. However, as no antibody assay offers 100% specificity, and the results are strongly dependent on the assay method used to measure the autoantibodies, it is essential to use assay methods with high diagnostic specificity, to minimize false positives and obtain a high positive predictive value. This review examines the various autoantibodies for which a role in predicting the development of an autoimmune disease has been demonstrated in long-term prospective studies.