The internal circadian clock adapts slowly, if at all, to rapid transitions between different shift schedules. This leads to misalignment (desynchrony) of rhythmic physiological systems, such as sleep, alertness, performance, metabolism and the hormones melatonin and cortisol, with the imposed work-rest schedule. Consequences include sleep deprivation and poor performance. Clock gene variants may influence tolerance of sleep deprivation. Shift work is associated with an increased risk of major disease (heart disease and cancer) and this may also, at least in part, be attributed to frequent circadian desynchrony. Abnormal metabolism has been invoked as a contributory factor to the increased risk of heart disease. There is recent evidence for an increased risk of certain cancers, with hypothesized causal roles of light at night, melatonin suppression and circadian desynchrony. Various strategies exist for coping with circadian desynchrony and for hastening circadian realignment (if desired). The most important factor in manipulating the circadian system is exposure to and/or avoidance of bright light at specific times of the 'biological night'.