Frailty is increasingly recognized as a geriatric syndrome that shares common biomedical determinants with rapid muscle fatigue: aging, disease, inflammation, physical inactivity, malnutrition, hormone deficiencies, subjective fatigue, and changes in neuromuscular function and structure. In addition, there is an established relationship between muscle fatigue and core elements of the cycle of frailty as proposed by Fried and colleagues (sarcopenia, neuroendocrine dysregulation and immunologic dysfunction, muscle weakness, subjective fatigue, reduced physical activity, low gait speed, and weight loss). These relationships suggest that frailty and muscle fatigue are closely related and that low tolerance for muscular work may be an indicator of frailty phenotype.