Heterotopic ossification is characterized by the formation of normal bone at ectopic soft-tissue locations. Regardless of the etiology of heterotopic ossification, requisite pathogenetic conditions include an inductive signal capable of stimulating morphogenesis, a population of inducible osteoprogenitor cells, and a heterotopic environment conducive to osteogenesis. Two rare heritable and developmental forms of heterotopic ossification, fibrodysplasia ossificans progressiva and progressive osseous heteroplasia, provide valuable clinical and pathogenetic insights into heterotopic ossification in humans. A fundamental understanding of the developmental and molecular pathology of these disorders may lead to more effective strategies for preventing and treating heterotopic ossification in humans.