This chapter provides an overview of osteogenesis imperfecta (OI), a congenital connective tissue disorder characterized by severe osteoporosis and bone fragility. OI is the most common inherited connective tissue disorder, affecting approximately 25,000-50,000 people in the United States. The chapter discusses the classification of OI, clinical features, and differential diagnosis, highlighting the distinction between dominant and recessive forms of the disease. It also covers the management and treatment of OI, including the use of bisphosphonates and surgical interventions. The molecular genetics of dominant and recessive OI is explored, detailing the roles of genes such as COL1A1, COL1A2, CRTAP, LEPRE1, PPIB, FKBP10, SERPINH1, and SERPINF1 in the pathogenesis of the disease. Additionally, the chapter reviews mouse models that mimic various forms of OI, providing insights into the genetic basis and clinical manifestations of the disorder.This chapter provides an overview of osteogenesis imperfecta (OI), a congenital connective tissue disorder characterized by severe osteoporosis and bone fragility. OI is the most common inherited connective tissue disorder, affecting approximately 25,000-50,000 people in the United States. The chapter discusses the classification of OI, clinical features, and differential diagnosis, highlighting the distinction between dominant and recessive forms of the disease. It also covers the management and treatment of OI, including the use of bisphosphonates and surgical interventions. The molecular genetics of dominant and recessive OI is explored, detailing the roles of genes such as COL1A1, COL1A2, CRTAP, LEPRE1, PPIB, FKBP10, SERPINH1, and SERPINF1 in the pathogenesis of the disease. Additionally, the chapter reviews mouse models that mimic various forms of OI, providing insights into the genetic basis and clinical manifestations of the disorder.