Relating physiological variables on an organ system level to metabolic function within the intracellular environment has been exceedingly difficult because of a paucity of techniques. Most of the tools at our command necessitate either the removal or destruction of tissues before measurements can be made. Recently, NMR spectroscopy has been applied to several important questions relating organ system and cellular physiology. NMR has the distinct advantage of being noninvasive and nondestructive, allowing the investigator to make repetitive measurements of intracellular variables while manipulating experimental variables that are important on the organ system level. In this review we shall present several examples of such NMR investigations so that the reader will gain some appreciation of the potential of this relatively new technique. Cellular acid-base homeostatic mechanisms, high-energy phosphate metabolism, and regulation of anaerobic glycolysis will be discussed for such diverse cellular populations as mammalian brain, mammalian heart muscle, salamander skeletal muscle, amphibian skin, and invertebrate muscle. In addition, the role of phosphomonoesters and phosphodiesters in lipid metabolism for several tissues in different species will be evaluated.