The islets of Langerhans consist of endocrine cells embedded in a network of specialized capillaries that regulate islet blood flow. Despite evidence for a critical role of islet perfusion in endocrine pancreas function, there is information to support no fewer than three models of endocrine cell perfusion, emphasizing the lack of a universally accepted physiological theory. Islet blood flow is regulated by signals, such as hormones and nutrients that reach the islet vasculature from distant tissues via the bloodstream. In addition, islet perfusion determines communication between endocrine and exocrine cells and between different types of endocrine cells within islets. Interest in islet microcirculation has increased after improvements in islet transplantation, a therapy for diabetes mellitus that requires revascularization of grafted islets in a new host organ. Abnormal revascularization is thought to be partly responsible for differences in graft and native islet function. Similarly, angiogenesis has been shown to be a critical step in the transformation of islet hyperplasia to neoplasia.