Abstract: The extreme conditions causing fatigue in military service members in combat and combat training deserve special consideration. The collective effects of severe exertion, limited caloric intake, and sleep deprivation, combined with the inherent stressors of combat, lead to both physiological and psychological fatigue that may significantly impair performance. Studies of combat training have revealed a myriad of endocrine, cognitive, and neurological changes that occur as a result of exposure to extreme conditions. Further contributory effects of multiple military deployments, post-traumatic stress disorder, and traumatic brain injury may also influence both the susceptibility to and expression of fatigue states. Further research is needed to explore these effects to enhance military readiness and performance as well as prevent injuries.