This paper reviews the association between neurobiologically-based sleepiness/fatigue and human-error related accidents. It concludes that fatigue contributes to human error and accidents in technology-rich, industrialized societies in terms of human, environmental and economic impacts. The cultural utilization of time as expressed in 24-h work operations, combined with the widespread use of automation, will continue to escalate in the next century, further increasing the risks of fatigue-related accidents, as more people conduct vigilance-based activities at times other than the traditional daytime work hours. Fatigue management and prevention of fatigue-related catastrophes need to become a sustained priority for government, industries, labour, and the public. Scientific data are urgently needed on the most likely areas in which sleepiness-related performance failures contribute to accidents, and on the effectiveness of a wide range of potentially useful countermeasures.