Conventional immunological methods for the detection of serum autoantibodies have been an essential tool for the diagnosis of autoimmune diseases for 40 years: in the last decade autoantibody tests have become accepted criteria for the diagnosis and classification of the main systemic and organ-specific autoimmune diseases. The high degree of purification reached by the autoantigens used in these methods has allowed high diagnostic sensitivity and specificity, especially in the case of some new autoantibodies of particular clinical significance, such as anti-nucleosome, anti-transglutaminase, anti-TSH receptor and anti-citrullinated protein autoantibodies. In the last 5 years the advent of proteomic technology, which allows the simultaneous measurement of a number of autoantibodies (multiplexing), has opened up new horizons in the diagnosis of autoimmune diseases. Multiplexing is particularly interesting for clinical laboratories, for organisational, logistical/managerial, physiopathological and research reasons. The emerging technologies are represented by systems based on planar or non-planar (suspension) arrays: the latter include methods which use addressable microbeads or nanobarcoded particles. Within a few years, the new methods will allow testing of individual autoantibody profiles, which will probably improve understanding of the physiopathology of autoimmunity, allow early diagnosis (due to the predictive value of autoantibodies), and drive the diffusion of antigen-specific therapies in autoimmune diseases.