Orexin, also known as hypocretin, is a neuropeptide crucial for the regulation of sleep–wake states. Emerging evidence indicates that the orexinergic system also plays a pivotal role in cognitive and emotional functions, yet a comprehensive synthesis of these findings is lacking. In this review, we first summarize the neurocircuitry and molecular mechanisms by which the orexinergic system regulates cognition and emotion under physiological conditions. We then focus on how dysfunction of the orexinergic system contributes to cognitive and affective impairments in aging and neurodegenerative diseases. Finally, we discuss the therapeutic potential of targeting the orexinergic system to enhance cognitive and emotional function. We propose that modulating orexinergic system to increase arousal levels represents a key strategy for improving cognition and emotion. Advancing research in this area will deepen our understanding of orexin function and enrich theoretical frameworks linking arousal, cognition, and emotion.