Hereditary hemorrhagic telangiectasia (HHT) of Rendu-Osler-Weber disease is a multi system vascular dysplasia characterized by the presence of multiple telangiectasias, mainly affecting mucosal tissue and arterial-venous connections. It commonly affects lungs, liver and central nervous system. Bleeding is the most common symptom and its treatment can be surgical or pharmacological. We herein review the systemic therapy that attempts to minimize bleeding as well as blood transfusion therapy. Blood therapy and fibrinolytic treatment especially aminocaproic acid and tranexamic acid are discussed. Danazol, hormone therapy and other less common drugs used in the treatment of HHT are also reviewed.