The Edmonton trials have brought about a marked improvement in the short-term rate of success of islet transplantation with rates of insulin-independence of 80% at 1-year being reported by several institutions worldwide. Unfortunately, this rate consistently decreases to 10-15% by 5 years post-transplantation. Several mechanisms have been proposed to explain this apparent 'islet exhaustion', but are difficult to pinpoint in a given patient. Understanding the reasons for islet graft exhaustion and its kinetics is a prerequisite for the improvement of islet transplantation outcome. In this regard, efficient monitoring tools for the islet graft have been conspicuously lacking and are required to detect islet damage and diagnose its mechanisms in a timely fashion, so as to initiate salvage therapy such as antirejection treatment. Tools for the monitoring of the islet graft include follow-up of metabolic function but mostly indicate dysfunction when it is too late to take action. Progress is likely to arise in the fields of immune monitoring, molecular monitoring and islet imaging, notably thanks to magnetic resonance (MR) or positron emission tomography (PET) technologies.