The brain has long been viewed as an insulin-insensitive organ. Following the demonstration of insulin receptors in the brain, this assumption has been challenged, and a whole new field of research has emerged. Insulin appears to play a role in brain physiology, and disturbances of cerebral insulin signalling and glucose homeostasis are implicated in brain pathology. This special issue of the European Journal of Pharmacology provides an overview of research into the involvement of glucose and insulin in the modulation of cognition and synaptic plasticity in health and in disease. In three sections, the effects of glucose and insulin on the brain will be discussed from a physiological perspective, in relation to brain ageing and Alzheimer's disease, and in relation to diabetes mellitus, respectively. These subjects will be covered from various angles, from the level of molecular neurosciences, to the level of applied neuropsychology.