Acute coronary syndrome (ACS) is a group of clinical syndromes with high morbidity and mortality worldwide. Increasing evidence suggest that plaque erosion with an intact fibrous cap is one of the major causes responsible for ACS. Basic experiments have shed light on the unique molecular characteristics of plaque erosion. It has been indicated that plaque erosion starts with the changes of blood flow disturbance-induced endothelial cell damage, resulting in loss of basement membrane integrity and endothelial cell desquamation, with consequent formation of neutrophil extracellular traps and thrombosis. This review will discuss the molecular characteristics of atherosclerotic plaque erosion and translational research needed for future precision medicine in patients with plaque erosion.