Central nervous system hypersomnias (narcolepsy type 1 and type 2, idiopathic hypersomnia, and Kleine-Levin syndrome) are orphan sleep disorders in which the predominant symptom is excessive daytime sleepiness. The evaluation of sleepiness requires rigorous clinical and neurophysiologic approaches that may include the Epworth Sleepiness Scale, multiple sleep latency tests, and the maintenance of wakefulness test. However, to date, no gold standard measurement of excessive sleepiness exists, and there are no quantifiable biologic markers. The main pathophysiologic feature of central hypersomnias is thought to reflect a deficiency of arousal systems, rather than an overactivity of sleep systems or an imbalance between those systems. Impaired neurotransmission of hypocretin/orexin (neuropeptides of the lateral hypothalamus) is involved in the neurobiology of narcolepsy with cataplexy (NT1). NT1 is a well-characterized disorder, due to the destruction of hypocretin/orexin neurons by a probable autoimmune process. The biologic hallmarks of the other central hypersomnias remain unknown, and neurophysiologic biomarkers are still of major importance for the diagnosis and characterization of those disorders.