Technical Abstract: Skeletal muscle represents the largest organ in the body regardless of age or sex. It is the major determinant of energy use at rest and during physical activity. These considerations have rekindled interest in characterizing the advantages and limitations of methods to determine human whole-body and regional muscle mass in health and disease. A wide variety of methods are available to determine muscle mass. They range in complexity from simple, low-cost measurements including the combination of limb circumferences and skinfold thicknesses and application of low-level alternating current to the use of costly radiological techniques such as computed tomography and magnetic resonance imaging. This review provides a description of the physical bases of each method, the accuracy and precision of the estimates, applications, and practical considerations such as cost and availability. Experimental hypotheses necessitate which method is selected for use. This information will be useful to biomedical researchers who seek to determine muscle mass in studies to characterize differences among age, sex and population groups and responses to interventions such as diet, exercise and medical therapies.