In this chapter, we discuss the key-role of heparin in the prophylaxis and treatment of venous thromboembolism (VTE) and other thrombotic disorders. Heparin exerts its antithrombotic effects by facilitating the ability of antithrombin (AT), a plasma serum protease inhibitor, to inhibit thrombin (factor IIa) and factor Xa. Different heparin formulations can be used for the prophylaxis of thrombosis and treatment, going from unfractionated heparin (UFH), different low-molecular-weight heparin (LMWH) preparations, to the recently introduced synthetic pentasaccharide fondaparinux. All heparin formulations can be administrated only by the parenteral route, including the intravenous (iv) and the subcutaneous (sc) route. We will overview the clinical evidence for the use of different heparin formulations in the prophylaxis and treatment of venous thromboembolism, of superficial vein thrombosis and of acute coronary syndromes (ACS). Special issues, like the use of heparins in pregnancy or in children, will also be discussed. Although heparin is an almost one century-old drug it remains a cornerstone of antithrombotic treatment.