IHS has traditionally been taught to be a rare and a diagnosis of exclusion. Given that many disorders can mimic IHS, and a previous absence of diagnostic features or biological markers specific to IHS, this is understandable. It is important to rule-out by history, sleep diary or actigraphy, depression and other affective disorders, insufficient sleep, and disturbance of circadian rhythms (e.g., advanced sleep phase syndrome and delayed sleep phase syndrome). In our experience, hypothyroidism and iron deficiency with or without anemia can also cause excessive sleep and daytime sleepiness and should be assessed for and corrected as appropriate. A night-time sleep test (polysomnogram) is performed followed by multiple sleep latency testing (MSLT) the day after during which the patient is given an opportunity to fall asleep on 4 or 5 occasions at 2-hour intervals after waking up. This testing performed at a sleep laboratory rules out other causes of sleepiness such as obstructive sleep apnea, and the MSLT in papoltients with IHS usually demonstrates an average latency to sleep of < 8 minutes, and the intrusion of dream sleep into 1 or fewer daytime naps. If the results do not paint a clear picture (e.g, narcolepsy is suggested in the absence of cataplexy, or there is a compelling history of excessive sleep, sleepiness, or ostensible hypovigilance with the psychomotor vigilance test in the presence of a normal or ambiguous MSLT) we will often perform a lumbar puncture to obtain cerebrospinal fluid (CSF) in order to measure hypocretin, and determine to what extent a patient’s CSF might enhance GABA receptor function in human cells grown in a petri dish in the laboratory. Thus, we have discovered that the CSF of many subjects with IHS, narcolepsy without cataplexy, and others requiring extraordinary amounts of sleep (e.g, > 70 hours/week termed ‘long sleepers’) exhibit an increased ability to enhance function of the inhibitory and sleep promoting chemical, GABA. These observations suggest a common cause to these disorders that have traditionally been considered as separate and unique, and in fact, supports their consideration as a single entity which in the proposed revisions to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) will be termed major hypersomnolence disorder (Figure 2).