The paper gives an overview of the problems to be tackled nowadays by occupational health with regards to shift work as well as the main guidelines at organizational and medical levels on how to protect workers’ health and well-being. Working time organization is becoming a key factor on account of new technologies, market globalization, economic competition, and extension of social services to general populations, all of which involve more and more people in continuous assistance and control of work processes over the 24 hours in a day. The large increase of epidemiological and clinical studies on this issue document the severity of this risk factor on human health and well being, at both social and psychophysical levels, starting from a disruption of biological circadian rhythms and sleep/wake cycle and ending in several psychosomatic troubles and disorders, likely also including cancer, and extending to impairment of performance efficiency as well as family and social life. Appropriate interventions on the organization of shift schedules according to ergonomic criteria and careful health surveillance and social support for shift workers are important preventive and corrective measures that allow people to keep working without significant health impairment.