The concept of chemical individuality was introduced by Garrod in 1908. Inheritance of Mendelian traits including disease states has finally reached a new level of understanding based on the modern principles of gene expression coupled with new insight into the metabolism of RNA species and protein. Over 300 different perturbations in metabolite profiles with their identifying alteration(s) in protein and/or gene structure and/or function have been identified in the past 100 years. With the realization in 1953 that the sentinel disease, phenylketonuria, can be effectively treated by nutritional manipulation tailored to the needs of each individual, we have essentially entered a new phase in metabolic medicine, namely that of nutritional therapeutics. The infant destined for a lifetime of cognitive and motoric handicaps may be rescued by the implementation of a nutritional prescription in early development. Patients with inherited defects that impact on intermediary metabolism need to receive nutritional therapy on an individualized basis. Metabolic profiling, i.e., the array of small molecules or analytes, as well as large macromolecules, measured with precision in body fluids or tissues, can be used to devise a nutritional therapeutic plan, as well as serve as endpoints to evaluate the biochemical efficacy of intervention.