Natural-abundance 13C nuclear magnetic resonance (NMR) spectroscopy is a noninvasive technique that enables in vivo assessments of muscle and/or liver glycogen concentrations. When directly compared with the traditional needle biopsy technique, NMR was found to be more precise. Over the last several years, we have developed and used 13C-NMR to obtain information about human glycogen metabolism both under conditions of altered blood glucose and/or insulin and with exercise. Because NMR is noninvasive, we have been able to obtain more data points over a specified time course, thereby dramatically improving the time resolution. This improved time resolution has enabled us to document subtleties of the resynthesis of muscle glycogen after severe exercise that have not been observed previously. An added advantage of NMR is that we are able to obtain information simultaneously about other nuclei, such as 31P. With interleaved 13C- and 31P-NMR techniques, we have been able to follow simultaneous changes in muscle glucose-6-phosphate and muscle glycogen. In this article, we review some of the work that has been reported by our laboratory and discuss the relevance of our findings for the management of diabetes.