Fracture care and osteogeneic response deviate significantly from normal in patients with traumatic brain injury (TBI) or spinal cord injury (SCI). In TBI open reduction and internal fixation (ORIF) are recommended whenever possible to improve mobilization in the face of spasticity and the formation of heterotopic ossification (HO). In the patient with SCI, immobility and paralysis negatively alter healing. A fracture above the level of SCI, although not altered in healing, when treated by ORIF will facilitate transfer training and self care. Lower extremity fractures in SCI have a high incidence malunion, delayed union, or nonunion and are best treated by internal fixation. HO occurs in 11% of TBI patients, with the hip, shoulder, and elbow being common sites. Trauma dramatically increases the incidence of HO. In SCI, the incidence of HO is 20%, with most occurring in the hip region. A genetic predisposition to form HO is suspected but not proven.