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Neuropeptide S (NPS), a new peptide possessing 20 amino acid residues, is one of the most recent examples of a neurotransmitter identified by the orphan receptor strategy. NPS selectively binds and activates an orphan G-protein-coupled receptors (GPCRs), named NPS receptor (NPSR). NPS and NPSR mRNA are expressed in the brain regions, such as locus coeruleus (LC), lateral parabrachial nucleus (LPBN), dorsal medial nucleus of thalamus, hypothalamus and amygdaloid nucleus. NPS induces behavioral arousal and promotes wakefulness by suppressing all stages of sleep. Further studies about effect of the NPS system in sleep and wake might help to discover a potential target for pharmacological treatment of sleep disorders. <br />