<p>Pain management in the intensive care unit represents one of the most challenging aspects of critical care medicine. Critically ill patients frequently experience severe pain from their underlying conditions, invasive procedures, and prolonged immobilisation. Traditional opioid-centric approaches, while effective for acute pain control, have increasingly been associated with significant adverse effects, including respiratory depression, delirium, ileus, immunosuppression, and the development of tolerance and dependence. The paradigm shift toward multimodal analgesia combines pharmacological agents from different classes with non-pharmacological interventions to optimise pain relief while minimising opioid consumption and related complications. This comprehensive review examines the evidence supporting multimodal analgesia strategies in critically ill patients, explores the mechanisms underlying synergistic analgesic effects, and provides practical guidance for implementation in diverse ICU populations. Through analysis of contemporary literature and clinical trials, this paper demonstrates that multimodal approaches not only reduce opioid requirements but also improve patient outcomes, including decreased duration of mechanical ventilation, shorter ICU length of stay, and reduced incidence of delirium.</p>