Postoperative pain is a complex and multifactorial symptom that requires a thoughtful approach using a variety of treatment modalities to obtain an optimal outcome after surgery. Multimodal (or 'balanced') analgesia represents an approach to preventing postoperative pain where the patient is administered a combination of opioid and non-opioid analgesic drugs that act at different sites within the central and peripheral nervous systems in an effort to minimize opioid use and, therefore, to decrease opioid-related side effects. Despite widespread interest in this concept from both the anesthesia and surgery communities, very few prospective, randomized, controlled clinical investigations have been conducted that utilize this approach to improving patient comfort and facilitating recovery after surgery. Most of the published studies focus on the effects of a single therapeutic modality when it is added to an existing analgesic regimen. More recently, clinical investigators have begun to examine the beneficial effects of combined multimodal approaches in preventing postoperative pain by utilizing combinations of non-opioid analgesics to minimize the opioid analgesic requirements and opioid-related side effects. This review explores the theoretical basis for multimodal analgesia and the existing scientific evidence supporting its benefit in improving pain control after surgery. Recent investigations that have examined the impact of this therapeutic approach for improving clinically meaningful patient outcomes after surgery will be discussed.