This chapter provides an overview of heparin, including discovery, structure, mechanism of action, and principal use for anticoagulation. For over 100 years, heparin has a central role in prophylaxis and treatment of prothrombotic states, be it used in the event of pulmonary embolism or maintaining blood fluidity during dialysis. Indeed, heparin had a role in enabling the development of cardiopulmonary bypass for the surgical treatment of cardiopulmonary diseases. The development of heparin depolymerization which produced low molecular weight heparin further enhanced the usefulness of this anticoagulant, where this type of heparin can be self-administered. There has been much written about heparin over the last century, and this chapter provides a concise overview.