Reciprocal signalling between the endothelium and the pancreatic epithelium is crucial for coordinated differentiation of the embryonic endocrine and exocrine pancreas. In the adult pancreas, islets depend on their dense capillary network to adequately respond to changes in plasma glucose levels. Vascular changes contribute to the onset and progression of both type 1 and type 2 diabetes. Impaired revascularisation of islets transplanted in individuals with type 1 diabetes is linked to islet graft failure and graft loss. This review summarises our understanding of the role of vascular endothelial growth factor-A (VEGF-A) and endothelial cells in beta cell development, physiology and disease. In addition, the therapeutic potential of modulating VEGF-A levels in beta and beta-like cells for transplantation is discussed.