Type 1 (insulin-dependent) diabetes mellitus is a frequent chronic disease that affects children as well as adults. The disease keeps a life-long burden on patients, their environment and society. Although still incompletely understood, its pathogenesis becomes progressively unravelled. Autoimmune phenomena play an important role, be it as underlying cause or as consequence or innocent bystanders of another primary event. Much of the present knowledge on environmental and genetic triggers for the slow islet beta-cell destruction culminating in clinically overt disease has been acquired through national diabetes registries. The latter represent confidential data- and blood sample banks that collect epidemiological, clinical and biological information from as many new cases as possible within a given area. These registries operate along international guidelines and offer a worldwide framework for optimizing prediction of clinically overt disease in individuals at risk by means of specialized clinical biological tests, carried out in reference laboratories under international quality control surveillance. Better understanding of pathogenesis and predictability of Type 1 diabetes also creates perspectives for disease prevention. Collaborative efforts of national registries provide the methodology of choice to assess the effectiveness of proposed pharmacological or immunological interventions. Several international trials are being contemplated for the near future. Clinical biology will play an important role for selection of the subjects and their further monitoring.