Metabolomics is a new approach based on the systematic study of the full complement of metabolites in a biological sample. This technology consists of two sequential steps: (1) an experimental technique, based on mass spectrometry or nuclear magnetic resonance (NMR) spectroscopy, designed to profile low molecular weight compounds, and (2) multivariate data analysis. Metabolomic analysis of biofluids or tissues has been successfully used in the fields of physiology, diagnostics, functional genomics, pharmacology, toxicology and nutrition. Recent studies have evaluated how physiological variables or pathological conditions can affect metabolomic profiles of different biofluids in pediatric populations. Little is known about the overall metabolic status of the term and preterm neonate. On the other hand, the management of sick or preterm newborns might be improved if more information on perinatal/neonatal maturational processes and their metabolic background were available. At present, the use of metabolomics in Neonatology is still in the pioneering phase. Meaningful diagnostic information and simple, non-invasive collection techniques make urine a particularly suitable biofluid for metabolomic approach in neonatal medicine. Using NMR-based metabolomic analysis of urine, distinct metabolic patterns have been shown to be associated with different classes of gestational age in a population of preterm and term infants. Together with genomics and proteomics, metabolomics appears to be a promising tool in Neonatology for the monitoring of postnatal metabolic maturation, the identification of biomarkers as early predictors of outcome, the diagnosis and monitoring of various diseases and the "tailored" management of neonatal disorders.