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Acute pain after orthopedic surgery is an almost universal patient experience. Approaches to the treatment of acute pain have changed in response to patient satisfaction considerations and the shift toward outpatient surgery and early discharge from the hospital. Pain relief has been improved with new drugs and new modes of delivery and timing. Many of these advances are based on a greater understanding of the neural pathways and mechanisms involved in the stages of acute pain. The knowledge that the tissue response to acute pain further increases pain has led to the strategy of preventing pain before it is perceived, termed pre-emptive analgesia. Nonsteroidal anti-inflammatory drugs, local anesthetics, adrenergic agents, and novel methods of applying opioids have been added to conventional parenteral analgesics, both for improved pain relief and, when administered before surgery, to achieve pre-emptive analgesia. Combinations of treatments may achieve improved pain control with decreased side effects. This paper briefly reviews the mechanisms of acute pain and treatment strategies in orthopedic patients, particularly pre-emptive analgesia, and reviews specific reports of the treatment of acute pain in orthopedic patients.