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Skeletal muscle size is an important factor in assessing adaptation to exercise training and detraining, athletic performance, age-associated atrophy and mobility decline, clinical conditions associated with cachexia, and overall skeletal muscle health. Magnetic resonance (MR) imaging and computed tomography (CT) are widely accepted as the gold standard methods for skeletal muscle size quantification. However, it is not always feasible to use these methods (e.g., field studies, bedside studies, and large cohort studies). Ultrasound has been available for skeletal muscle examination for more than 50 years and the development, utility, and validity of ultrasound imaging are underappreciated. It is now possible to use ultrasound in situations where MR and CT imaging are not suitable. This review provides a comprehensive summary of ultrasound imaging and human skeletal muscle size assessment. Since the first study in 1968, more than 600 articles have used ultrasound to examine the cross-sectional area and/or volume of 107 different skeletal muscles in more than 27,500 subjects of various ages, health status, and fitness conditions. Data from these studies, supported by decades of technological developments, collectively show that ultrasonography is a valid tool for skeletal muscle size quantification. Considering the wide-ranging connections between human health and function and skeletal muscle mass, the utility of ultrasound imaging will allow it to be employed in research investigations and clinical practice in ways not previously appreciated or considered. [ABSTRACT FROM AUTHOR]