Acute compartment syndrome is a surgical emergency that can threaten life and the limb. Moreover, lower extremity compartment syndrome is most commonly associated with high-energy mechanisms of injury; however, a high index of suspicion should be maintained with low-energy or penetrating trauma, vascular or crush injuries, and prolonged periods of immobility. Rare presentations are even documented in association with diabetes mellitus, hypothyroidism, malignancy, viral-induced myositis, nephrotic syndrome, and bleeding disorders. Most practitioners associate lower extremity compartment syndrome with the leg, but other sites including the buttock, thigh, and foot can develop the same pathology. Serial physical examinations by an experienced provider remain the best tool for accurate diagnosis, while intramuscular compartment pressure measurements are best used as an adjunct especially when a complete physical examination is not possible. Compartment syndrome, unlike many musculoskeletal conditions, is much easier to treat than to accurately diagnose. Prompt fasciotomies with release of all involved muscular compartments prevent the life- and limb-threatening sequelae of a missed compartment syndrome. Although fasciotomies are associated with increased blood loss and elevated risk of infection and commonly require split-thickness skin grafts in lieu of closure, they prevent irreversible ischemic tissue loss and potential for lifetime disability.