There are immediate and long-lasting harmful consequences to the nervous system when infants experience severe or repetitive pain. These effects are especially significant in preterm infants, who are vulnerable to neurological damage during this critical time of neurodevelopment. Painful experiences may cause structural and physiological changes within the nervous system. Repeated painful procedures may result in decreased pain thresholds and hypersensitivity to pain. Immediate harmful effects of pain include physiologic instability and increased incidence of serious complications such as intraventricular hemorrhage. Painful stressors may lead to sleep disturbances, feeding problems, and inability to self-regulate. Long-term effects of pain may include altered pain perception, chronic pain syndromes, and somatic complaints. Repetitive pain in the preterm infant may be associated with attention deficit disorders, learning disorders, and behavioral problems in later childhood. Nursing involvement with pain management is crucial to achieve positive health outcomes for high-risk infants and older children and adults who have experienced repetitive or severe pain as infants.