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Skeletal muscle is a large compartment that can now be quantified using research and clinically applicable regional and whole-body methods. The most important advances are the two imaging methods, computed tomography (CT) and magnetic resonance imaging (MRI). Both CT and MRI can serve as regional and whole-body reference methods when evaluating other approaches for estimating skeletal muscle mass. Imaging methods also afford the opportunity to quantify both anatomic skeletal muscle and the smaller adipose-tissue free skeletal muscle component. Other available methods for estimating skeletal muscle, either regional or at the whole body level, include dual-energy x-ray absorptiometry, in vivo neutron activation analysis-whole body counting, anthropometry, ultrasound, bioimpedance analysis, and urinary metabolite markers. Each method is reviewed in the context of the aging process, cost, availability, practicality, and desired accuracy. New insights should be possible when skeletal muscle mass, measured using these methods, is combined with other descriptors of muscle biochemical and mechanical function.