Air travel is a common mode of transportation in today’s society, particularly for individuals traveling long distances. Sleep disturbances associated with air travel frequently result in cognitive and physiologic impairments that may be detrimental to the traveler’s experience and intent. A primary consequence of air travel is the development of acute sleep deprivation, which may result in reduced attention/vigilance, alteration in mood states, diminished memory processing, and alteration in executive function. Along with and contributing to acute sleep deprivation, circadian rhythm misalignment resulting in jet lag disorder (JLD) is frequently encountered by air travelers traversing multiple time zones. JLD is characterized by insomnia or excessive daytime sleepiness associated with physical or mental impairment associated with travel. This review focuses on the neurocognitive manifestations of acute sleep deprivation and the pathophysiology and treatment of JLD to provide the practicing clinician a greater understanding of the sleep abnormalities manifest in air travelers. Treatment recommendations for the traveler, including the use of light/melatonin therapy, sleep scheduling, and pharmacologic aids for both sleep and alertness, are provided.