Drug therapy for dissolution of formed clots is a first-line approach in the treatment of myocardial infarction and thrombotic stroke. In addition, drug therapy for inhibition of the intrinsic and extrinsic pathways in the blood clotting cascade is used widely in ambulatory, acute care, and intensive care settings. Many health care providers mistakenly view these therapeutic approaches as identical. The authors review the physiology of intrinsic and extrinsic pathways in the blood clotting cascade and present the essential differences between anticoagulant and thrombolytic therapies.