Hypocretins/orexins are novel HYPOTHALAMIC neuropeptides involved in various HYPOTHALAMIC mechanisms, such as energy homeostasis and neuroendocrine function. Orexins A (33 amino acids) and B (28 amino acids) are derived from a single pre-pro-orexin polypeptide. Physiological studies over the last ten years have implicated orexin signaling plays a central role in a variety of important biological processes. There is a clear evidence for defects in orexin signaling being involved in obesity and diabetes, narcolepsy, panic anxiety disorder and drug addiction. Therefore, this system may be a potentially important therapeutic target for treatment of sleep disorder, obesity, emotional stress, and addiction. In addtion, it has been well known that orexin-A elicits analgesia. Thus, there is a considerable interest in the drug industry in the development of potent compounds for the manipulation of orexin signaling. Therefore, This a review about recent progress in understanding orexin system.