Multiple diseases have a strong metabolic component, and metabolomics as a powerful phenotyping technology, in combination with orthogonal biological and clinical approaches, will undoubtedly play a determinant role in accelerating the understanding of mechanisms that underlie these complex diseases determined by a set of genetic, lifestyle, and environmental exposure factors. Here, we provide several examples of valuable findings from metabolomics-led studies in diabetes and obesity metabolism, neurodegenerative disorders, and cancer metabolism and offer a longer term vision toward personalized approach to medicine, from population-based studies to pharmacometabolomics.