The disturbance of immune tolerance, often exemplified by the appearance of antibodies that bind to autologous normal proteins, is known to be an important pathogenetic mechanism in many widespread diseases. Thus, identification of the autoantibody repertoire has emerged as an important diagnostic approach. In this paper we addressed the value of the autoantibodies as predictors of the diseases and the descriptors of the disease course. Even though relevant information is scarce it has become clear that alterations in the immune status, accompanied by changes in the autoantibody repertoire, in numerous cases precede the clinical onset of a disease by many years. Furthermore, the course and prognosis of the diseases involving autoimmune mechanisms could be predicted by presence of specific autoantibodies. Thus, in addition to analysis of genetic information, evaluation of the autoantibody spectrum is anticipated to become a key tool in the coming era of precision medicine.