This volume describes the current state of our knowledge on the neurobiology of muscle fatigue, with consideration also given to selected integrative cardiorespiratory mechanisms. Our charge to the authors of the various chapters was twofold: to provide a systematic review of the topic that could serve as a balanced reference text for practicing health-care professionals, teaching faculty, and pre-and postdoctoral trainees in the biomedi cal sciences; and to stimulate further experimental and theoretical work on neurobiology. Key issues are addressed in nine interrelated areas: fatigue of single muscle fibers, fatigue at the neuromuscular junction, fatigue of single motor units, metabolic fatigue studied with nuclear magnetic resonance, fatigue of the segmental motor system, fatigue involving suprasegmental mechanisms, the task dependency of fatigue mechanisms, integrative (largely cardiorespiratory) systems issues, and fatigue of adapted systems (due to aging, under-and overuse, and pathophysiology). The product is a volume that provides compre of processes that operate from the forebrain to the contractile proteins.