New advances in antithrombotic therapy include low-molecular weight heparins (LMWHs), heparinoids, and direct thrombin inhibitors. LMWHs and heparinoids have improved pharmacologic and pharmacokinetic properties compared with standard, unfractionated heparin. LMWHs are effective in preventing venous thromboembolism in general surgical patients, orthopedic patients, and general medical patients. At equipotent antithrombotic doses, LMWHs produce less bleeding than does unfractionated heparin. When given in fixed doses subcutaneously in the treatment of venous thromboembolic disease, LMWHs have been shown to be as effective as or more effective than and safer than standard heparin given intravenously with regular monitoring. Recent studies have demonstrated that LMWHs are effective in reducing the risk of death and myocardial infarction in patients with unstable angina; they are as effective as intravenous heparin when given subcutaneously without monitoring. Preliminary data indicate that LMWHs also may be effective in improving outcomes in patients with ischemic stroke. The pharmacokinetic characteristics of LMWHs permit their use in a fixed dose administered subcutaneously without monitoring, resulting in greater clinical utility than standard heparin. The direct thrombin inhibitors have a narrow safety window, and in doses that do not produce excessive bleeding have not been shown to have greater efficacy than that of unfractionated heparin.