Type 1 diabetes (T1D) is an autoimmune disease in which the insulin-producing beta-cells are destroyed. Islet or pancreas transplantation can restore insulin secretion and are established therapies for subgroups of T1D patients. Long-term insulin-independence is, however, hampered by recurrent autoimmunity and rejection. Accurate monitoring of these immune events is therefore of critical relevance for the timely detection of deleterious immune responses. The identification of relevant immune biomarkers of allo- and autoreactivity has allowed a more accurate monitoring of disease progression and responses to therapy at early stages, allowing proper therapeutic intervention, and possibly improvements in the success rate of islet and pancreas transplantation. This review describes the tools established and validated to monitor immune correlates of auto- and alloreactivity that associate with clinical outcome and identifies challenges that current immunosuppression strategies trying to preserve islet graft function face.