Behavior representations in simulation environments have become increasingly sophisticated as computational power and understanding of human cognitive processes have increased. Despite improvements in the breadth and depth of models of human behavior, comparatively little research has explored how human cognition is moderated by external and internal factors. In this review paper, we focus on fatigue, a pervasive cognitive moderator that has dramatic and sometimes tragic effects on human cognitive functioning. We discuss prior and current research investigating models of how fatigue impacts human cognition and behavior, sometimes leading to dramatic degradations. The paper ends with a description of our on-going efforts to identify mechanisms for fatigue within the Adaptive Control of Thought - Rational (ACT-R) cognitive architecture. Our approach involves integrating diverse research areas, especially biomathematical modeling of the effects of fatigue on neurobehavioral functioning, and computational cognitive modeling of human cognition and behavior.