Orexin’s role in human cognition has recently been emphasized and emerging evidences indicate its close relationship with Alzheimer’s disease (AD). This review aimed to demonstrate recent research on the relationship between orexin and AD. Orexin’s role in stress regulation and memory is discussed, with significant findings related to sexual disparities in stress response, with potential clinical implications pertaining to AD pathology. There are controversies regarding the orexin levels in AD patients, but the role of orexin in the trajectory of AD is still emphasized in recent literatures. Orexin is also accentuated in the context of tau pathology, and orexin as a potential therapeutic target for AD is frequently discussed. Future directions with regard to the relationship between orexin and AD are suggested: 1) consideration for AD trajectory in the measurement of orexin levels, 2) the need for objective measure such as polysomnography and actigraphy, 3) the need for close observation of cognitive profiles of orexin-deficient narcolepsy patients, 4) the need for validation studies by neuroimaging 5) the need for taking account sexual disparities in orexinergic activiation, and 6) consideration for orexin’s role as a stress regulator. The aforementioned new perspectives could help unravel the relationship between orexin and AD.