The anticoagulant drugs which are available currently — coumarins and heparins — are reasonably effective but are insufficiently specific and often inconvenient to manage. An improved understanding of the physiology of blood coagulation and its control mechanisms has led to the identification of target enzymes for novel, specific and potentially safer antithrombotics. These targets include the pivotal coagulation enzyme thrombin as well as other enzymes and co-factors within the tissue factor dependent coagulation pathway. In addition, analogues of physiological anticoagulants hold promise as therapeutic agents. It is likely that the range of drugs available for the management of thrombosis will expand over the next decade. There is the very real possibility of the introduction of orally active agents which may be used in fixed dosage regimens with no requirement for laboratory monitoring.