Hypophosphatasia (HPP) is a rare genetic metabolic bone disorder that is underdiagnosed. Although there are many forms of this disease, based on age of onset, symptoms, and severity, HPP is characterized by low serum alkaline phosphatase levels, bone fractures, and dental complications. Diagnosis of HPP is made from clinical, laboratory, and radiologic findings. Genetic testing for an ALPL gene variant responsible for causing HPP confirms a molecular diagnosis. Distinguishing HPP from other more common bone disorders, such as osteoporosis, is important as the treatment for these diseases differs greatly. Although there is no known cure for HPP, treatment should be holistic and multidisciplinary.