Over the past two decades, host-response biomarkers have been extensively used by clinicians for a better understanding of normal biological processes, the complexity and severity of illnesses, or pharmacological responses to therapeutic intervention. A myriad of information can be drawn from the gender, age, dietary intake and the disease history of an individual. These biomarkers may be promising for the complete phenotyping of a cell, tissue or an organism. In neonatology, these molecular markers may help in prediction of disease severity and its outcome, thus allowing personalized interventions. In this Review, existing data in the literature on metabolites in plasma, urine and maternal milk that may offer a unique insight into the host's dynamic behavior in different neonatal conditions will be examined.