Publisher Summary Osteogenesis imperfecta (OI) is a highly variable heritable disease of bone characterized by recurring bone fractures. It is the most common single gene defect causing bone disease. Three degrees of deforming OI, types II, III, and IV, are associated with decreasing severity of growth retardation and limb deformity and all result from a mutation affecting the structure of the type 1 collagen molecule. This chapter provides an update to the well-described clinical classifications and points out recent advances in the diagnosis and therapy of the disease. It also reviews the consequences of mutations of type 1 collagen on the structure of the collagen fibers. Following this, it explains the biology of the osteoblast. Based on the understanding of the biology, it establishes the pathophysiology of the resulting bone disease. Furthermore, it emphasizes how this information influences the understanding of osteoporosis and other heritable diseases of connective tissue. In addition, it presents outstanding problems requiring further research attention, particularly relating to cell and somatic gene therapy. Finally, it discusses the therapy of OI using anti-resorptive agents.