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Type 1 diabetes (T1D) is one of the most common and severe chronic diseases affecting both children and adults. The aetiology of the disease remains unknown, and thus far no ‘true’ cure for those affected is available. Indeed, exogenous insulin replacement therapy to manage glucose metabolism to the best degree possible remains the current standard of care. However, despite a recent array of truly impressive improvements designed to enhance disease management (e.g. insulin analogues, continuous glucose monitoring, insulin pumps), it is still difficult for the vast majority of patients to reach recommended target HbA1C levels (< 7·0%). As a result of suboptimal disease management, far too many patients with T1D have an increased risk for disease-associated complications such as nephropathy, neuropathy and retinopathy, as well as hypoglycaemia. New treatment modalities are therefore needed urgently to bring a ‘true’ cure (disease prevention/disease reversal) to patients with T1D. Here we consider issues that collectively pose a major stumbling block in T1D research with respect to identifying a means to prevent and/or cure the disease. We begin this Perspective by discussing new insights emanating from studies of the pancreas in human T1D; findings which may, at least in part, explain why previous interventions seeking disease prevention/reversal have yielded insufficient benefit. We then turn to suggestions that could optimise the outcome of future clinical trials. Finally, we direct attention to recommendations for the global T1D research community; messages we deem to have the potential to improve our chances of finding the elusive T1D ‘cure’.