The growth hormone/insulin-like growth factor I (GH/IGF-I) axis is an important regulator of brain function which view is based on the evidence that 1) GH and IGF-I can cross the blood brain barrier, 2) GH and IGF-I can bind to sites in various brain structures, including the hippocampus, 3) GH can alter the dopamine turnover in the hippocampus and IGF-I the acetylcholine release, and 4) GH and IGF-I can activate the NMDA receptor in the hippocampus. These mechanisms may underlie the relationship between the GH/IGF-I axis and cognitive functioning. A reduced activity of the GH/IGF-I axis seems associated with cognitive dysfunction in adult patients with GH deficiency (GHD), Prader-Willi syndrome, traumatic brain injury (TBI), dementia and also with age-associated cognitive decline in healthy elderly. Moreover, IGF-I deficiency may be involved in the aetiology of schizophrenia. Treatment with GH appears to have a beneficial effect on cognitive functions in patients with GHD, Prader-Willi and TBI. However, as evidence of GH replacement on cognition in distinct groups is limited and diet, exercise, and specific medicines have known effects on the GH/IGF-I axis, future studies on the relationship between GH-, diet-, exercise-, or medication-induced GH/IGF-I increase and cognition are required.