The most common underlying cause of the acute coronary syndromes is atherosclerotic plaque rupture, which is therefore of major clinical and pathological importance. Further insight into the aetiology of plaque rupture is essential to the development of new therapeutic strategies. A suitable animal model would therefore be extremely useful, and such models have recently begun to be developed. As with animal models of other human diseases, no single model of plaque rupture is ideal. The available large animal models are essentially established models of atherosclerosis, with novel but merely descriptive characteristics of plaque vulnerability applied, and the small animal models of induced or spontaneous plaque vulnerability and rupture have the limitation that the lesions formed are usually in non-coronary vessels. Despite these limitations, it is becoming clear that the use of genetically modified mice – particularly apolipoprotein E knockout mice – is making it possible to investigate the pathogenesis of plaque rupture and to test potential new therapies.