Individuals vary in their thrombotic response to vascular injury. The reasons for this are numerous, involving heterogeneity in multiple platelet responses. Platelet research has tended to focus on functioning at the molecular level, and many experiments reflect results obtained in isolated, in vitro systems. However, platelets function in a complex and dynamic in vivo environment with the potential for a wide range of biological influences. This article reviews the evidence for diversity in platelet responses and the implications for individual variability in propensity to arterial thrombosis. Three overarching phenomena are considered. First, platelets can vary quantitatively and qualitatively in their responses to agonists. Second, platelets appear to have different intrinsic levels of procoagulant activity. Third, responses to various procoagulant, regulatory, and mediating factors likewise differ within and among individuals and can be influenced by blood-borne factors. These phenomena may help to explain differences in experimental arterial thrombosis observed in individuals.