Unfractionated heparin has historically been used as the anticoagulant of choice in the management of a number of thrombotic diseases. Recognition of the limitations of heparin has led to the development of a newer class of anticoagulants, the direct thrombin inhibitors. Argatroban is a synthetic small molecule that selectively inhibits thrombin at its active site. In preclinical studies, argatroban has been shown to be more effective than heparin in preventing arterial thrombosis and in promoting vessel patency in conjunction with thrombolysis in a number of animal models. In clinical trials, argatroban has been shown to be as effective as heparin in the management of ST-segment elevation myocardial infarction in conjunction with thrombolysis. It has been shown to be an effective anticoagulant in patients undergoing percutaneous coronary interventions. In patients with heparin-induced thrombocytopenia and heparin-induced thrombocytopenia complicated by thrombosis, argatroban significantly decreases the risk of thrombotic events. Small studies have demonstrated a potential role for its use in ischemic stroke and hemodialysis. Additional studies are warranted to confirm argatroban's efficacy in a wide variety of clinical settings.