Natural selection has evolved a process of fracture healing that is characterized by callus formation and is enhanced by physical loading and motion at the fracture site. Internal fixation of fractures alters the biology of fracture healing, especially when rigid fixation using plates is performed. Intramedullary nails that allow some motion and loading usually are associated with callus formation. Plates that practically eliminate interfragmentary motion, however, prevent external periosteal callus formation. Primary osteonal healing can occur with plate fixation, but if interfragmental gaping of greater than 1 mm exists, delayed healing occurs. Closed treatment of fractures occasionally results in nonunion. In addition, physicians' high expectations for skeletal restoration have prompted vigorous research in areas of bone grafting, graft substitutes, and analysis of local and systemic factors that regulate fracture healing. A better understanding of the activity of bone morphogenetic protein and growth factors, such as transforming growth factor beta, will allow manipulation of the biology of healing to enhance the surgical treatment of skeletal trauma.