Trauma is a significant health problem and a leading cause of death in all age groups. Pain related to trauma is frequently severe, but is often undertreated in the trauma population. Opioids are widely used to treat pain in injured patients but have a broad range of undesirable effects in a multitrauma patient such as neurologic and respiratory impairment and delirium. In contrast, regional analgesia confers excellent site-specific pain relief that is free from major side effects, reduces opioid requirement in trauma patients, and is safe and easy to perform. Specific populations that have shown benefits (including morbidity and mortality advantages) with regional analgesic techniques include those with fractured ribs, femur and hip fractures, and patients undergoing digital replantation. Acute compartment syndrome is a potentially devastating sequela of soft-tissue injury that complicates high-energy injuries such as proximal tibia fractures. The use of regional anesthesia in patients at risk for compartment syndrome is controversial; although the data is sparse, there is no evidence that peripheral nerve blocks delay the diagnosis, and these techniques may in fact facilitate the recognition of pathologic breakthrough pain. The benefits of regional analgesia are likely most influential when it is initiated as early as possible, and the performance of nerve blocks both in the emergency room and in the field has been shown to provide quality pain relief with an excellent safety profile.