OBJECTIVE This review introduces physiologists and clinical investigators to an ever-widening array of nuclear magnetic resonance applications. In particular, it highlights a multiple tracer technique that provides a comprehensive picture of metabolic processes within human liver. RESULTS Magnetic resonance spectroscopy is an important technique for studying metabolism in the brain, liver, heart and skeletal muscle. One fundamental advantage is that the studies are inherently noninvasive, so time-dependent information can be obtained. For example, 31P nuclear magnetic resonance investigations indicate that greater maximal oxygen uptake and oxidative capacity in trained athletes can be partially attributed to adaptations enhancing the rates at which phosphocreatine and inorganic phosphate recover during stress. In-vivo measurements of lipids and glycogen by 1H and 13C spectroscopy demonstrate that accumulation of intracellular lipids and impaired rates of glycogen synthesis contribute to insulin resistance and type 2 diabetes mellitus. Similar techniques can be used to analyze blood and urine samples obtained during administration of 2H or 13C tracers to yield information that cannot be easily obtained by mass spectrometry. Additional information available from nuclear magnetic resonance yields a comprehensive picture of liver metabolic pathways from a single clinical study. CONCLUSIONS A variety of magnetic resonance spectroscopy protocols have been validated and exploited for clinical studies, but relatively few investigators are comfortable with technical aspects of these protocols and utilize them for clinical research. Increased interaction between spectroscopists and other investigators is needed if the potential of nuclear magnetic resonance for studying in-vivo metabolism is to be fully realized.