Hypophosphatasia (HPP) is a rare inborn, metabolic bone disorder caused by mutations in the tissue-nonspecific alkaline phosphatase-encoding gene: ALPL. The diagnosis is based on biochemical, clinical and genetic evaluation. Low levels of ALP is a hallmark in diagnosing HPP. Mild forms may present unspecific symptoms and be more frequent than previously assumed. Adults with HPP may present with low bone mass, however, bisphosphonates are contraindicated for these patients. Finally, enzyme replacement therapy has opened new therapeutic perspectives regarding severe HPP.