Narcolepsy is characterized by excessive sleepiness and abnormal manifestations of rapid eye movement (REM) sleep. Neurochemical studies of human and canine narcolepsy have demonstrated disturbed monoaminergic and cholinergic function and suggest that deficits of noradrenaline availability in specific brain regions may account for much of its disordered pathophysiology. Genetic susceptibility to narcolepsy is closely linked to a specific region of the major histocompatibility complex on chromosome 6 and an important direction for future research will be to unravel the relationship between this gene region and the neurochemical abnormalities of narcolepsy.