Sleep is a complex behaviour whose precise physiological functions are unknown. Traditionally, it was believed that sleep is only for the brain, but increasingly, the role of sleep in other organs has been recognized. Recently the role of sleep duration and sleep disorders in the regulation of metabolism is increasingly appreciated. The hypothalamus, which is a major regulator for homeostatic regulatory mechanisms, is also a major regulator of sleep and wakefulness allowing integration of sleep, appetite, and metabolism. In particular, the lateral hypothalamic orexin (hypocretin) neurons have been shown to play a key role in wakefulness, appetite regulation, glucose sensing, locomotor activity and energy expenditure. The importance of hypothalamic integration of sleep and metabolism has been shown in both animals and also humans who suffer from the sleep disorder, narcolepsy. Narcolepsy is a profound neurological sleep disorder that results in excessive daytime sleepiness, but is also associated with obesity and insulin resistance. Patients with narcolepsy have undetectable orexin (hypocretin) neuropeptide levels in their cerebrospinal fluid and post-mortem studies have shown that orexin (hypocretin) mRNA expression is absent in hypothalami from patients with narcolepsy. Data from large population studies show that both long and short sleep duration are associated with obesity, the metabolic syndrome, diabetes, cardiovascular disease and mortality. These studies have been carried out across all age groups, and in several countries and ethnic groups. In a study of over 1000 individuals, short sleep duration was shown to be associated with greater body mass index but lower levels of the adipocytokine hormone leptin and higher levels of the stomach-derived hormone ghrelin. Low leptin and high ghrelin levels are a powerful appetite stimulatory signal. Data from other population studies suggest a relationship between sleep duration and physical activity. Human sleep laboratory studies have shown that both short sleep duration and sleep disruption are associated with metabolic derangements that are associated with the metabolic syndrome and diabetes. These studies also report associations between shorter sleep and energy expenditure. The objective of the presentation will be to discuss data available regarding the relation between sleep, metabolism and obesity including potential neurohormonal mechanisms.