While time of day, interacting with an individual’s chronotype, can have an important impact upon performance and health, severe disruption of the circadian system adds another level of complexity and severity. ‘When timing goes wrong’ considers the effects of flying across multiple time zones, resulting in jet lag, and shift work on human health. Sleep and circadian rhythm disruption is almost always associated with poor health. Four circadian rhythm sleep disorders have been identified: advanced sleep phase disorder, delayed sleep phase disorder, freerunning, and irregular sleep timing. Sleep and circadian rhythm disruption in mental illness and neurodegenerative disease is also discussed.