The islets of Langerhans are critical for glucose homeostasis but fail in diabetes, accompanied by autoimmune destruction of beta-cells in type 1 diabetes and increased insulin demand and beta-cell exhaustion in type 2 diabetes. During the last decade, there have been major advances not only in the molecular understanding of beta-cell stress, unfolded protein response, dedifferentiation, aging and failure, but also in counteracting mechanisms, such as beta-cell maturation, compensation, redifferentiation, autophagy and recovery. This meeting will address unresolved gaps in how these mechanisms intersect and how to shift fundamental insights into possible approaches and therapies to reverse diabetes. In parallel, this meeting will address how we can combine primary islets, differentiated stem cells or regenerative mechanisms with immune-evasive strategies for beta-cell replacement in type 1 diabetes. In development, the different niches that enable beta-cells to develop, mature and function are another important aspect of islet biology. In the adult, insulin secretion and progression/reversal of either type of diabetes can also be affected by inter-organ crosstalk, e.g. between the islet and the gut or brain. This Keystone meeting welcomes presentations on all aspects of islet biology, as well as from researchers at any career stage and from both academia and industry. A fusion of technical advances and novel biological concepts will encourage interdisciplinary collaborations of global nature to accelerate diabetes research.