Type 1 diabetes is an autoimmune disorder leading to loss of pancreatic β-cells and insulin secretion, followed by insulin dependence. Islet and whole pancreas transplantation restore insulin secretion. Pancreas transplantation is often performed together with a kidney transplant in patients with end-stage renal disease. With improved immunosuppression, immunological failures of whole pancreas grafts have become less frequent and are usually categorized as chronic rejection. However, growing evidence indicates that chronic islet autoimmunity may eventually lead to recurrent diabetes, despite immunosuppression to prevent rejection. Thus, islet autoimmunity should be included in the diagnostic work-up of graft failure and ideally should be routinely assessed pretransplant and on follow-up in Type 1 diabetes recipients of pancreas and islet cell transplants. There is a need to develop new treatment regimens that can control autoimmunity, as this may not be effectively suppressed by conventional immunosuppression.