Narcolepsy is known to be a complex disorder; both genetic and environmental factors play a role in its pathophysiology. Although narcolepsy presents one of the tightest association with a specific HLA antigen (DQB1*0602), there is strong evidence that non-HLA genes also confer susceptibility, both monoaminergic and hypocretinergic systems seem to be involved and may interfere with the phenotype. Implication of the hypocretin system is well-established in both canine and murine narcolepsy (caused by mutation) and a consistent reduction in hypocretin neuron seems to be the cause of human narcolepsy. An autoimmune process is probable.