This chapter reviews a series of metabolomic studies carried out in previous years on the utility and application of nuclear magnetic resonance (NMR)-based metabolomics in an attempt to understand pathophysiological mechanisms in obesity and diabetes. The first part focuses on several methodological concerns that are critical to blood plasma ¹H NMR experimental design in clinical, biobank and multicentre research settings. Variations in sample collection, preparation and storage within the field of clinical metabolomics might hamper the effective implementation of ¹H NMR spectroscopy. We describe and comment on specific precautions or improvements that should be taken into account at each experimental stage when performing ¹H NMR-based metabolomics research on plasma samples. Next, we discuss the application of ¹H NMR-metabolite phenotyping in the context of childhood obesity and diabetes. NMR-based metabolomics offers a complementary tool to traditional screening in order to more accurately and comprehensively identify metabolic risk profiles. In the end, more targeted and effective screening and intervention strategies for obesity and early-onset diabetes can be developed.