Methods of treatment are different for acute and chronic pain. For acute pain, analgesics such as nonsteroidal anti-inflammatory drugs and opiates are commonly used, sometimes combined with regional anesthesia, such as peripheral nerve block or peridural local anesthesia. The mechanism of transition from an acute to a chronic pain state is poorly understood. Only NMDA receptor antagonists and epidural morphine have shown relatively consistent results as preemptive analgesics. Agents more successfully used to manage chronic pain include those that modify the neurochemistry of the spinal cord dorsal horn, such as tricyclic antidepressants, anticonvulsants, γ-amino butyric acid agonists, local anesthetic analogs, and NMDA antagonists. Opiates may be used chronically, but tolerance and lack of efficacy may then develop. In selected patients with refractory chronic pain, centrally administered analgesics may be considered, including opiates, dilute local anesthetic, NMDA receptor antagonists, clonidine, midazolam, baclofen, or calcium channel blockers. For both acute and chronic pain, a single agent may be less effective than combinations of analgesics with different mechanisms of action.