Biomarkers are useful tools for research into type 1 diabetes (T1D) for a number of purposes, including elucidation of disease pathogenesis, risk prediction, and therapeutic monitoring. Susceptibility genes and islet autoantibodies are currently the most useful biomarkers for T1D risk prediction. However, these markers do not fully meet the needs of scientists and physicians for several reasons. First, improvement of the specificity and sensitivity is still desirable to achieve better positive predictive values. Second, autoantibodies appear relatively late in the disease process, thus limiting their value in early disease prediction. Third, the currently available biomarkers are not useful for assessing therapeutic outcomes because some are not involved in the disease process (autoantibodies) and others do not change during disease progression (susceptibility genes). Therefore, considerable effort has been devoted to the discovery of novel T1D biomarkers in the last three decades. The advent of high-throughput technologies for genetic, transcriptomic, and proteomic studies has allowed genome-wide examinations of genetic polymorphisms, global gene changes, and protein expression changes in T1D patients and prediabetic subjects. These large-scale studies resulted in the discovery of a large number of susceptibility genes and changes in gene and protein expression. While these studies have provided a number of novel biomarker candidates, their clinical benefits remain to be evaluated in prospective studies, and no new “star biomarker” has been identified until now. Previous studies suggest that significant improvements in study design and analytical methodologies have to be made to identify clinically relevant biomarkers. In this review, we discuss progress, opportunities, challenges, and future directions in the development of T1D biomarkers, mainly by focusing on the genetic, transcriptomic, and proteomic aspects.