The circadian system regulates the cyclical occurrence of wakefulness and sleep through a series of oscillatory networks that comprise two different theoretical processes. The suprachiasmatic nucleus (SCN) of the hypothalamus contains the master oscillatory network necessary for coordinating these daily rhythms, and in addition to its ability to robustly generate rhythms, it can also synchronize to environmental light cues. During jet lag, abrupt shifts in the environmental light-dark cycle temporarily desynchronize the SCN and downstream oscillatory networks from each other, resulting in increased sleepiness and impaired daytime functioning. Polysomnographic data show that not only does jet lag result in changes of sleep-wake timing, but also in different aspects of sleep architecture. This type of circadian misalignment can further lead to a cluster of symptoms including major metabolic, cardiovascular, psychiatric, and neurological impairments. There are a number of treatment options for jet lag involving bright light exposure, melatonin, and use of hypnotics, but their efficacy greatly depends on their time of use, the length of time in the new time zone, and the specific circadian disturbance involved. The aim of this review is to provide mechanistic links between the fields of sleep and circadian rhythms to understand the biological basis of jet lag and to apply this information to clinical management strategies.