The circadian clock regulates rhythms at the molecular, physiological and behavioral levels, to adapt to the daily cycles of environmental factors. Desynchronization of circadian rhythms with the external environmental cues causes circadian misalignment with detrimental effects on health and cognition. Rapid travelling across the time zones and social factors such as night work and shift work leads to jet lag and desynchronization between the central and peripheral clocks and between the internal rhythms with the environment. Owning to industrialization, more and more people experience travelling or social jet lag, the effects of circadian misalignment and its impacts on physiology, metabolism, immune and behavior should be taken into account. The advances in molecular mechanisms underlying circadian clock furthered our understanding jet lag, and a number of physical and pharmacological measures as well as social treatments regarding diet, sleep and rest management are developed to alleviate or counter the circadian misalignment and related symptoms. In this review, we summarized the comprehensive features of the circadian clock system, the effects of jet lag and social jet lag on health and performance, and the treatment strategies of jet lag.