Severe extremity trauma is a significant cause of morbidity and disability; these injuries are often considered for amputation. Two studies have shown few differences between amputation and limb salvage outcomes. Functional limitations that result from loss of muscle needed to cover bone and provide limb function are a major factor in the decision to amputate a salvaged limb. Several studies have reported successful management of muscle loss with soft-tissue transfer. Extracellular matrix scaffolds and muscle regeneration using stem cells are promising technologies. However, no single strategy has proved to be effective in the management of limb pain following extremity trauma; a multimodal approach is required for best results. Additional knowledge gaps exist, such as the effect of occupational and physical therapy on the outcome of severe limb injury, factors such as peer visitation and social support networks, and the effect of sex, cultural differences, and patient personality.