Cholinergic neurones in the CNS undergo complex changes during normal aging. In recent years, considerable attention has focussed on the neurotrophins and, in particular, nerve growth factor, as potential maintenance factor for cholinergic-neurone function, and as therapeutic agents for use in a variety of neurodegenerative disorders including Alzheimer's disease. While brain cholinergic neurones from the neonate to the aged respond to nerve growth factor with enhanced expression of transmitter phenotype, there appears to be an age-related, region-specific decline in responsiveness. This age-related decrement in neurotrophin action might play a role in dysfunction of cholinergic neurones, and cognitive loss, and could limit the use of these factors as therapeutic agents.