Polymorphisms within genes encoding endogenous mediators of inflammation are good candidates for the individual differences in systemic inflammatory responses of neonates to infection. Ina similar manner, polymorphisms in the genes encoding drug metabolizing enzymes, drug transporters, and drug receptors can influence a neonate's risk of an adverse drug reaction or can alter the efficacy of drug treatment. Additionally, molecular tools are proving valuable in the diagnosis of neonatal infection. This article gives an overview of the genetic susceptibility to sepsis, discusses the use of molecular genetics in diagnostic tests for infection, and reviews the potential for more effective and specific therapies for sepsis based on genetic variability.