Islet transplantation, an important approach to achieve insulin independence for individuals with type 1 diabetes, is limited by the lack of accurate biomarkers to track beta-cell death post islet infusion. In this review, we will discuss existing and recently described biomarkers. As beta cells are killed by the immune system, fragments of beta cell-specific cell-free DNA and proteins are released into the periphery. Several different strategies to identify these fragments have been described. Some circulating, non-coding microRNAs, particularly miRNA-375 are also showing potential to reflect the rate of beta cell loss post-clinical islet transplantation. Recent advances in identifying accurate beta cell-specific biomarkers such as differentially methylated insulin cell-free DNA and circulating miRNA-375 may help predict clinical outcomes. More studies are required to examine the robustness of these biomarkers to detect chronic beta-cell loss in islet transplantation recipients.