Fatigue is a major safety concern in many fields, but especially in transportation, because fatigue can result in disastrous accidents. Fatigue is considered an internal precondition for unsafe acts because it negatively affects the human operator's internal state. Research has generally focused on pilots, truck drivers, and shift workers.
Fatigue can be a symptom of a medical problem, but more commonly it is a normal physiological reaction to exertion, lack of sleep, boredom, changes to sleep-wake schedules (including jet lag), or stress.
Fatigue can be both physical and mental. Physical fatigue is the inability to continue functioning at the level of one's normal abilities; a person with physical fatigue cannot lift as heavy a box or walk as far as he could if not fatigued.
Mental fatigue, on the other hand, rather manifests in sleepiness or slowness. A person with mental fatigue may fall asleep, may react very slowly, or may be inattentive. With microsleeps, the person may be unaware that he was asleep. Without proper amount of sleep, it will feel like certain tasks seem complicated, concentration will drop and ultimately result in fatal mistakes
The Federal Motor Carrier Safety Administration identifies three main factors in driver fatigue: Circadian rhythm effects, sleep deprivation and cumulative fatigue effects, and industrial or "time-on-task" fatigue.
In addition to the primary factors identified by the FAA, other potential contributors to fatigue during transportation have been identified. These include endogenous factors such as mental stress and age of the vehicle operator, as well as exogenous or environmental stressors, such as the presence of non sea-level cabin pressure in-flight, vehicle noise, and vehicle vibration/acceleration (which contributes to the sopite syndrome). Many of the exogenous contributors merit further study because they are present during transportation operations but not in most lab studies of fatigue.
The International Civil Aviation Organization (ICAO) that codifies standards and regulations for international air-navigation defines fatigue as: "A physiological state of reduced mental or physical performance capability resulting from sleep loss or extended wakefulness, circadian phase, or workload (mental and/or physical activity) that can impair a crew member's alertness and ability to safely operate an aircraft or perform safety related duties." 
Human factors are the primary causal factor aviation accidents. In 1999, the National Aeronautics and Space Administration, NASA, testified before the U.S. House of Representatives that pilot fatigue impacts aviation safety with "unknown magnitude". The report cited evidence of fatigue issues in areas including aviation operations, laboratory studies, high-fidelity simulations, and surveys. The report indicates that studies consistently show that fatigue is an ongoing problem in aviation safety. In 2009, Aerospace Medical Association listed long duty work hours, insufficient sleep, and circadian disruptions as few of the largest contributing factors to pilot fatigue. Fatigue can result in pilot error, slowed responses, missed opportunities, and incorrect responses to emergency situations.
A November 2007 report by the National Transportation Safety Board indicates that air crew fatigue is a much larger, and more widespread, problem than previously reported. The report indicates that since 1993 there have been 10 major airline crashes caused by aircrew fatigue, resulting in 260 fatalities. Additionally, a voluntary anonymous reporting system known as ASAP, Aviation Safety Action Program, reveals widespread concern among aviation professionals about the safety implications of fatigue. The NTSB published that FAA's response to fatigue is unacceptable and listed the issue among its "Most Wanted" safety issues.
Safety experts estimate that pilot fatigue contributes to 15-20% of fatal aviation accidents caused by human error. They also establish that probability of a human factor accident increases with the time pilots are on duty, especially for duty periods of 13 hours and above (see following statements):
"It is estimated (e.g. by the NTSB) that fatigue contributes to 20-30% of transport accidents (i.e. air, sea, road, rail). Since, in commercial aviation operations, about 70% of fatal accidents are related to human error, it can be assumed that the risk of the fatigue of the operating crew contributes about 15-20% to the overall accident rate. The same view of fatigue as a major risk factor is shared by leading scientists in the area, as documented in several consensus statements." 
"For 10-12 hours of duty time the proportion of accident pilots with this length of duty period is 1.7 times as large as for all pilots. For pilots with 13 or more hours of duty, the proportion of accident pilot duty periods is over five and a half times as high. [...] 20% of human factor accidents occurred to pilots who had been on duty for 10 or more hours, but only 10% of pilot duty hours occurred during that time. Similarly, 5% of human factor accidents occurred to pilots who had been on duty for 13 or more hours, where only 1% of pilot duty hours occur during that time. There is a discernible pattern of increased probability of an accident the greater the hours of duty time for pilots." See. Federal Aviation Administration, Office of Aviation Policy and Plans, Washington, DC 20591, USA, March 2003.
Many countries regulate working hours for truck drivers to reduce accidents caused by driver fatigue. The number of hours spent driving has a strong correlation to the number of fatigue-related accidents. According to numerous studies, the risk of fatigue is greatest between the hours of midnight and six in the morning, and increases with the total length of the driver's trip.
Fatigue among doctors is a recognized problem. It can impair performance, causing harm to patients. A study using anonymous surveys completed by junior doctors in New Zealand found that 30% of respondents scored as "excessively sleepy" on the Epworth Sleepiness Scale and 42% could recall a fatigue related clinical error in the past 6 months
In the US, shift length is limited for nurses by federal regulation and some state laws.