Fibrodysplasia ossificans progressiva (FOP), or Münchmeyer's disease, is a rare, autosomal dominant genetic disorder, characterized by episodic progressive and cumulative heterotopic ossification, leading to a disabling metamorphosis into a “stone man”, with irremediable joint immobility, leaving families and health professionals often distraught, faced to the immeasurable progression of the disease. The involvement of a recurrent mutation of the activin-like kinase gene, ACVR1/ALK2 gene, an activating mutation of the (TGF)-β/BMP pathway, was demonstrated in 2006 by F. Kaplan, E. Shore and an international consortium. This major discovery has launched many research projects for understanding the pathophysiological basis and targeting specific therapies approaches. The present management of this pathology includes mainly preventive measures, and symptomatic treatment of disease flare-ups preceding the phenomenon of ossification, by various anti-inflammatory agents. Several innovative therapies are currently undergoing preclinical and clinical development, aimed at blocking the upstream and downstream signaling pathways of ACVR1/ALK2, marking a new era for the community of affected individuals and people engaged with FOP patients. Progressive osseous heteroplasia (POH) also belongs to the group of genetic disorders with extensive heterotopic ossification, characterized by the abnormal formation of bone within the connective tissues. It is an ultra-rare pathology (less than 100 cases described to date), severely progressive. This great rarity seems to be related to incomplete penetrance with wide variability of manifestations. The onset of ossification is episodic, as in FOP. On the other hand, these two conditions may be distinguished by the facts that POH is due to heterotopic ossification mainly of intramembranous origin, that there is no triggering factor leading to bone formation, there is no progression according to a characteristic pattern and by the absence of concomitant inflammatory factor. There is a direct differentiation of mesenchymal progenitors into osteoblasts. POH is associated with inactivating mutations of the GNAS gene. Treatments are currently limited to symptomatic measures, including ensuring cutaneous asepsis, adequate analgesia and non-steroidal anti-inflammatory drugs.