Although nuclear magnetic resonance (NMR) is well-established as a routine clinical imaging technique (magnetic resonance imaging or MRI), its application as a tool for metabolic investigations in humans is much less widespread in the medical community. To date, very few laboratories have combined the scientific interest, technical expertise (especially in vivo NMR spectroscopy), and facilities required to perform meaningful NMR studies of human metabolism. Among the few published reports of studies using in vivo NMR spectroscopy, diabetes mellitus, or more generally the physiology and pathophysiology of glucose homeostasis, is the dominant topic. This situation is related to the historical role of the Yale MR Center (R.G. Shulman, D.L Rothman) in the development of in vivo NMR, and to the collaboration of NMR methodologists with the Endocrinology Section of the Yale Medical School (G.I. Shulman). Thus, in the field of diabetes and metabolism, in vivo NMR has already contributed significantly to increasing our understanding of basic physiology as well as of pathophysiological mechanisms. This ''practical research note'' first describes the basic principles of in vivo NMR and provides practical information about the use of this technique in metabolic investigations. The metabolic parameters accessible through in vivo NMR are then reviewed and illustrated by a few examples from the literature.