Update This article was updated on July 22, 2015, because the name of one of the authors, Victor W. Wong, was listed incorrectly. The name, which previously read "Victor C. Wong," on pages 1101 and 1108, now reads "Victor W. Wong." An erratum has been published: J Bone Joint Surg Am. 2015 Sep 2;97(17):e59. ➤ Heterotopic ossification occurs most commonly after joint arthroplasty, spinal cord injury, traumatic brain injury, blast trauma, elbow and acetabular fractures, and thermal injury. ➤ The conversion of progenitor cells to osteogenic precursor cells as a result of cell-mediated interactions with the local tissue environment is affected by oxygen tension, pH, availability of micronutrients, and mechanical stimuli, and leads to heterotopic ossification. ➤ Radiation and certain nonsteroidal anti-inflammatory medications are important methods of prophylaxis against heterotopic ossification. ➤ Well-planned surgical excision can improve patient outcomes regardless of the joint involved or the initial cause of injury. ➤ Future therapeutic strategies are focused on targeted inhibition of local factors and signaling pathways that catalyze ectopic bone formation.