Pain management, along with the prevention of infectious complications, is among the primary objectives of the perioperative period. In infants and newborns, intense pain triggers a stress response. In similar surgical interventions, the stress response activated by afferent neuronal impulses from the site of injury in newborns is greater in magnitude but shorter compared with that in adults. Effective analgesia with opioids during cardiac surgery has been shown to improve surgical outcomes. Prolonged, high-intensity pain in a newborn with ineffective analgesia leads to the progression of such pathological conditions as hypoxia, metabolic acidosis, impaired liver and kidney function, an increased risk of sepsis, disseminated intravascular coagulation, and higher neonatal mortality. At present, the capabilities of traditional analgesia methods remain limited. In this regard, the main approaches to improving the efficacy of pain management in pediatric practice include various regimens combining non-opioid analgesics, supplemented with opioids if necessary, as well as the development of new effective and safe pharmacologic agents with analgesic activity.