The atherosclerotic process is negatively affected by all the components of the haemostatic system (vascular, platelets, blood coagulation, fibrinolysis). The diseased coronary tree is a high shear rate flow system which, in turn, implies a high number of platelet collisions at sites of vascular injury. This a distinctive feature of coronary thrombosis and illustrates the relevance of blood rheology in thrombosis development. It is appalling how the clinical benefit derived from a conceptually simple intervention such as the partial inhibition of platelet function or blood coagulation is actually discernible by a crude tool such as a clinical trial. Almost all the subgroups take advantage from the treatment and coronary as well as non-coronary events are prevented. Although strong arguments exist for the chronic use of oral anticoagulants in patients with previous myocardial infarction, antiplatelet regimens are more attractive because they do not require any particular skill and are unlikely to determine haemorrhagic complications. New strategies in the chronic antithrombotic treatment of patients with coronary atherosclerosis may involve the pharmacologic manipulation of GpIIb/IIIa (or other platelet integrins) as well as the direct blockade of thrombin. However it is the combination of different antithrombotic agents that appears most promising presently. The combined use of antiplatelet and anticoagulant drugs has already been shown to be effective in acute coronary syndromes and in patients with prosthetic heart valves. It is hoped that the same pattern will be confirmed also in the chronic phase of coronary artery disease by ongoing clinical trials.