This report provides a practical guide and algorithm for the screening and subsequent management of neonatal hypoglycemia. Current evidence does not support a specific concentration of glucose that can discriminate normal from abnormal or can potentially result in acute or chronic irreversible neurologic damage. Early identification of the at-risk infant and institution of prophylactic measures to prevent neonatal hypoglycemia are recommended as a pragmatic approach despite the absence of a consistent definition of hypoglycemia in the literature.