Glucagon, secreted by the α-cells of the pancreatic islets, is the most important glucose-increasing hormone of the body. The precise regulation of glucagon release remains incompletely defined but has been proposed to involve release of inhibitory factors from neighbouring β-cells (paracrine control). However, the observation that glucose can regulate glucagon secretion under conditions when insulin secretion does not occur argues that the α-cell is also equipped with its own intrinsic (exerted within the α-cell itself) glucose sensing. Here we consider the possible mechanisms involved with a focus on ATP-regulated K⁺-channels and changes in α-cell membrane potential.