Pilot fatigue is a significant, but often under-reported problem in both civilian and military aviation operations. Although estimates vary, official statistics indicate that fatigue is involved in at least 4-8% of aviation mishaps, and surveys of pilots and aircrew members reveal that fatigue is an important concern throughout today's 24/7 flight operations. Regulatory efforts aimed at limiting flight hours and ensuring at least minimal periods of crew rest have to some extent mitigated fatigue-related difficulties in the cockpit, but it is clear that much remains to be done about this insidious threat to air safety. Scheduling factors, sleep deprivation, circadian disruptions, and extended duty periods continue to challenge the alertness and performance levels of both short-haul and long-haul pilots and crews. Solutions for these problems are not straightforward, but they can be developed through the cooperative efforts of scientists, regulators, managers, and the pilots themselves. Over the past 20 years, scientific understanding of human sleep, fatigue, and circadian rhythms has expanded considerably. The thorough integration of this new knowledge into modern crew-resource management practices will facilitate the establishment of optimal crew scheduling routines and the implementation of valid aviation fatigue countermeasures.