The objective of this review was to examine the evidence for the link between fatigue and safety, especially in transport and occupational settings. For the purposes of this review fatigue was defined as ‘a biological drive for recuperative rest’. The review examined the relationship between three major causes of fatigue– sleep homeostasis factors, circadian influences and nature of task effects – and safety outcomes, first looking at accidents and injury and then at adverse effects on performance. The review demonstrated clear evidence for sleep homeostatic effects producing impaired performance and accidents. Nature of task effects, especially tasks requiring sustained attention and monotony, also produced significant performance decrements, but the effects on accidents and/or injury were unresolved because of a lack of studies. The evidence did not support a direct link between circadian-related fatigue influences and performance or safety outcomes and further research is needed to clarify the link. Undoubtedly, circadian variation plays some role in safety outcomes, but the evidence suggests that these effects reflect a combination of time of day and sleep-related factors. Similarly, although some measures of performance show a direct circadian component, others would appear to only do so in combination with sleep-related factors. The review highlighted gaps in the literature and opportunities for further research.