Aspirin has been convincingly shown to reduce the incidence of vascular occlusive events in a wide range of patients at risk of thrombotic complications. These beneficial effects are currently linked to suppression of thromboxane A2-dependent platelet aggregation. This in turn reflects permanent loss of the cyclooxygenase activity of platelet prostaglandin G/H synthase, through acetylation of Ser530. Progress in our understanding of the molecular mechanism of action of aspirin and definition of the clinical pharmacology of its platelet effects has been associated with a downward trend in its daily dosage. This has been reduced by a factor of ten over the last decade, substantially reducing gastrointestinal toxicity, while leaving antithrombotic efficacy virtually unchanged. Carlo Patrono reviews the biochemical, pharmacological and clinical data that form the basis of the present consensus and provide a rationale for clinical trials of low-dose aspirin.