Hypocretin (orexin) neurotransmission is not only crucially involved in the regulation of sleep and wake, but serves in multiple autonomic and cognitive functions as well. This is reflected in the widespread connections between the hypothalamic hypocretin neurons and the rest of the brain, such as dense projections to the frontal cortex. Both frontal cognitive impairment and autonomic disturbances have been described in ALS. Furthermore, in some ALS patients there may be sleep disturbances other than sleep related breathing disorders, including REM sleep behaviour disorder. In addition, a role for the hypocretin system in the regulation of motor functions has been suggested. Hypocretin defects have been described in several neurodegenerative disorders. We therefore speculated that the hypocretin system is also involved in ALS and measured hypocretin-1 levels in cerebrospinal fluid samples from 20 patients. All results were well within the normal range (>200 pg/ml) and individual values showed no correlation with age, gender and disease duration. We conclude that it is unlikely that the hypocretin system is involved in the degenerative process of ALS.