Despite the dramatic reduction in cardiac events reported in the lipid lowering trial, a substantial body of evidence from sources as diverse as epidemiology, clinical trials and cell biology suggests that the atherogenesis involves processes far more complex than elevation in serum lipids (Table 1.1). Until the 1980s the central focus of pathologists was the debate over whether coronary thrombosis is a premortem or postmortem event. In the late 1980s, however, coronary angioscopy in symptomatic patients focused attention on plaque rupture. Angioscopy in patients at the time they were experiencing clinical syndromes definitively demonstrated that the culprit lesion in patients with stable angina was an atheroma with a smooth surface, whereas those with unstable angina had a disrupted endothelial surface, with or without thrombus formation. Although these data established the causal importance of intimal disruption in acute coronary syndromes, there was no understanding of its pathologic basis.