The assessment and management of perioperative pain in an intensive care setting is complex and challenging, requiring several patient-specific considerations. Administering analgesia is difficult due to interacting effects of pre-existing conditions, interventions, and deviation from standard levels of expressiveness of pain. A significant part of this complexity also arises from the reduced capacity of critically ill patients to fully communicate the severity and nature of their pain. We provide an overview of pharmacological approaches and regional techniques, which can be employed alongside the management of anxiety and sleep, to alleviate pain in the critically ill patients in the perioperative period. These interventions require additional assessments unique to critical care, yet achieving pain relief for improving clinical outcomes and patient satisfaction remains a constant.