Background：Orexins are a category of neuropeptides that are secreted by orexinergic neurons located exclusively in the perifornical area of lateral hypothalamus. Orexins have extensive functions in the brain, including modulations of feeding behavior, energy homeostasis, sleep and arousal, reward and emotion. They play a role in endocrine and cardiovascular systems as well. Recently, it is reported that orexins also take part in the modulation of learning and memory. Objective: To review the different viewpoints and recent progress of orexins in the regulation of learning and memory. Content: In this review, we briefly introduce the hippocampus pathway and the non-hippocampus pathway through which orexins modulate learning and memory, and the relationship between orexins and neurodegenerative diseases. Trend: The effects and mechanisms of orexins in learning and memory have not been entirely understood. Further researches may provide new ideas for the clinical treatment of postoperative cognitive dysfunction and neurodegenerative diseases.