Type 1 diabetes (T1D) research has made great strides over the past decade with advances in understanding the pathogenesis, natural history, candidate environmental exposures, exposure triggering time, disease prediction, and diagnosis. Major monitoring efforts have provided baseline historical measures, leading to better epidemiological studies incorporating longitudinal biosamples (ie, biobanks), which have allowed for new technologies ('omics') to further expose the etiological agents responsible for the initiation, progression, and eventual clinical onset of T1D. These new frontiers have brought forth high-dimensionality data, which have furthered the evidence of the heterogeneous nature of T1D pathogenesis and allowed for a more mechanistic approach in understanding the etiology of T1D. This review will expand on the most recent advances in the quest for T1D determinants, drawing upon novel research tools that epidemiology, genetics, microbiology, and immunology have provided, linking them to the major hypotheses associated with T1D etiology, and discussing the future frontiers.