Over the last 15 years, there has been a shift from unfractionated heparin to low-molecular-weight heparin or fondaparinux for many indications. Nonetheless, heparin continues to be used and it remains the drug of choice for selected indications and patients. This paper reviews when and how to use heparin and when low-molecular-weight heparin or fondaparinux may be a better choice. The paper also describes some of the new parenteral anticoagulants under development and provides perspective on how the introduction of rapid-acting oral thrombin or factor Xa inhibitors is likely to reduce or eliminate the need for bridging with parenteral anticoagulants.