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Magnetic resonance spectroscopy (MRS) is an imaging approach that allows for the noninvasive molecular characterization of a region of interest. By detecting signals of water, lipids, and other metabolites, MRS can provide metabolic information for lesion characterization and assessment of treatment response. Although MRS has been routinely used in the brain, clinical applications within the musculoskeletal system have only more recently emerged. The aim of this article is to review the technical considerations for performing MRS in the musculoskeletal system, focusing on proton MRS, and to discuss its potential roles in musculoskeletal tumor imaging and the assessment of muscle physiology and disease.