Pancreatic beta-cells are connected by gap junction channels made of a connexin protein, referred to as Cx36. Through these channels, beta-cells are coupled to each other, i.e. exchange cytoplasmic ions and small metabolites. Previous experiments have indicated that these exchanges are important for coordinating the function of individual cells within pancreatic islets, particularly with regard to glucose-induced insulin secretion. Advances in molecular biology, genetics and mouse transgenic approaches allow now for a direct experimental testing of this mechanism in vitro as well as in vivo. Recent experiments in rodent and culture models suggest that connexin-dependent cell-to-cell crosstalk is a significant player in the multifactorial regulation of insulin secretion and, possibly, of other beta-cell functions, such as growth. Elucidating the still obscure mechanism whereby connexin signalling exerts this influence will provide insights on the contribution of direct cell-to-cell interactions in the physiological regulation of beta-cell life. The presence of Cx36 within human pancreatic islets, raises the further challenge to determine whether a dysfunction of connexin signaling may contribute to the pathophysiology of beta-cell dysfunctions in type I and/or type II diabetes. Efforts to understand the functions of beta-cell connexins are also a prerequisite for the engineering of surrogate cells and their proper tridimensional packaging, which are instrumental for the future implementation of a replacement cell therapy in diabetic patients.