Type 1 diabetes (T1D) is an insulin-dependent form of diabetes resulting from the autoimmune destruction of pancreatic beta cells. The past few decades have seen tremendous progress in our understanding of the molecular basis of the disease, with the identification of susceptibility genes and autoantigens, the demonstration of several abnormalities affecting various cell types and functions, and the development of improved assays to detect and monitor autoimmunity and beta cell function. New findings about the disease pathology and pathogenesis are emerging from extensive studies of organ donors with T1D promoted by the JDRF nPOD (Network for the Pancreatic Organ Donor with Diabetes). Furthermore, the establishment of extensive collaborative projects including longitudinal follow-up studies in relatives and clinical trials are setting the stage for a greater understanding of the role of environmental factors, the natural history of the disease, and the discovery of novel biomarkers for improved prediction, which will positively impact future clinical trials. Recent studies have highlighted the chronicity of islet autoimmunity and the persistence of some beta cell function for years after diagnosis, which could be exploited to expand therapeutic options and the time window during which a clinical benefit can be achieved.