Multiple workplace xenobiotic, physical, and psychosocial factors can affect employee wellbeing and health, particularly when working nights. The human circadian time structure (CTS) is an unappreciated, yet potentially important consideration to establishing threshold limiting values, employee biological monitoring (BM) procedures, and recommended biological exposure indices (BEIs). Encounters by night workers, before CTS adjustment, to potentially harmful workplace contaminants and stressful physical conditions, occur during a different circadian stage than day workers. Numerous animal and human investigations document prominent circadian patterning in the biological tolerance to a broad array of chemical, biological, and physical stressors often found in occupational settings. Time-qualified for biological rhythms reference values, several currently utilised in clinical laboratory medicine, are likely to be of relevance to employee surveillance. Workplace psychosocial factors are additionally of great importance to employee wellbeing, with several demand-control-social support and effort-reward imbalance models serving to assess detrimental outcomes. Despite recognition the psychosocial workplace milieu can affect the physical and psychological health of dayworkers, there is a scarcity of knowledge of its impact on night and shift employees. Some studies indicate low job control, high physical demands, low supervisor social support, and high overcommitment can be more problematic for night than day shift workers. At-work violence is an additional psychosocial stress, with police officers, security personnel, bank employees, professional drivers, and other service employees in regular contact with the public, in particular, at elevated risk. The severity of workplace violence problems and their consequences is probably underestimated, especially when co-existing among stressors with known impact on workers´ health. Practical considerations and recommendations for action to mitigate the effect of these multiple job stressors of particularly high relevance to night and shift workers are presented.