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Delirium is a serious neuropsychiatric condition that emerges acutely in all age groups, including infants, children, and adolescents. Delirium serves as an urgent signal of distress that a young child's brain is in trouble. Prevention, recognition, and management of infants with delirium is often especially challenging due to their pre-verbal status and still immature cognitive development. This article presents an overview of delirium in infants, offers details regarding the presentation of delirium in infants, discusses the challenges to screening and identification of infants with delirium, and provides evidence-based suggestions for pediatric nurses to optimize nursing care for infants at risk for or exhibiting delirium.