Narcolepsy is a sleep disorder emerging in early adulthood on an HLA-related genetic background. Through unresolved pathways, involving the destruction or silencing of specific cells in the lateral hypothalamus, a deficiency of orexin production occurs. An autoimmune process targeting orexin-producing cells may cause acquired orexin deficiency. Abnormalities in cytokine production reported in narcolepsy unspecifically support this idea, but empirical evidence for a causative role of immunopathology is lacking. Orexin deficiency affects neuroendocrine and neurotransmitter systems leading to reduced stability of and/or disturbed transitions between wakefulness, REM, and nonREM sleep. However, narcolepsy is rather a complex neuroendocrine disorder rather than a pure sleep disorder because orexin deficiency induces endocrine and metabolic disturbances such as obesity and diabetes.