This review concentrates on discussing the various therapeutic agents available to prevent or inhibit clot formation. Particular emphasis is placed on therapies associated with modi®cation to coagulation factors, and the inhibitors of thrombin formation and action. The genesis of ischaemic cardiovascular disease is related to inappropriate platelet function and/or thrombin generation in excess amounts or at inappropriate sites. The most commonly used agents currently available to inhibit or slow thrombin production include vitamin K antagonists and heparin, acting through circulating or endothelial-derived intermediaries. More recently, a number of agents, which can act to directly inhibit thrombin, have been licensed for use in humans. It is expected that the range of these compounds will eventually grow to replace the use of unfractionated heparin (UFH) and vitamin K antagonists within the next few years. To better understand the mechanism of action of all of these compounds, a brief description of the mechanism of clot formation and the pivotal role of thrombin in this process is required together with the mechanisms for localizing and controlling this activity.