Shift work was positively associated with higher incidence of metabolic syndrome, obesity, cardiovascular disease, sleep disturbances, decreased immune functions, and cancer. Observed disorders were manifested usually after longer time of shift work (more than 10 years). On the other hand, disturbed daily profile of melatonin and cortisol during shift work were detected even in human self reporting well tolerated shift work. Similarly, changes in thyroid stimulating hormone, prolactin, growth hormone, insulin, and ghrelin were demonstrated. Changes in hormone concentrations are influenced by shift work, sleep or circadian system or combinations of above mentioned regulatory factors. The circadian system consists of the central part localized in the hypothalamus and peripheral oscillators located in all tissues of the body. The central oscillator is predominantly synchronized by light and peripheral oscillators are more responsive to metabolic signals. Under conditions of shift work, central and peripheral oscillators dissociate that causes misalignment of daily rhythms in physiological functions. Synchronization during shift work can be improved by melatonin supplementation and manipulation with light: dark cycles and food regimens. Shift work tolerance is individual. Partial positive selection can be achieved on the basis of several psychological traits. Appropriate schedule can be estimated on the basis of chronotype.